470 results on '"Zhou, Xiangtian"'
Search Results
152. Leber’s hereditary optic neuropathy is associated with mitochondrial ND1 T3394C mutation
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Liang, Min, primary, Guan, Minqiang, additional, Zhao, Fuxing, additional, Zhou, Xiangtian, additional, Yuan, Meixia, additional, Tong, Yi, additional, Yang, Li, additional, Wei, Qi-Ping, additional, Sun, Yan-Hong, additional, Lu, Fan, additional, Qu, Jia, additional, and Guan, Min-Xin, additional
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- 2009
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153. MicroRNA-34a Inhibits Uveal Melanoma Cell Proliferation and Migration through Downregulation of c-Met
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Yan, Dongsheng, primary, Zhou, Xiangtian, additional, Chen, Xiaoyan, additional, Hu, Dan-Ning, additional, Dong, Xiang Da, additional, Wang, Jiao, additional, Lu, Fan, additional, Tu, LiLi, additional, and Qu, Jia, additional
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- 2009
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154. Spontaneous Axial Myopia and Emmetropization in a Strain of Wild-Type Guinea Pig (Cavia porcellus)
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Jiang, Liqin, primary, Schaeffel, Frank, additional, Zhou, Xiangtian, additional, Zhang, Sen, additional, Jin, Xi, additional, Pan, Miaozhen, additional, Ye, Lingying, additional, Wu, Xiaomin, additional, Huang, Qinzhu, additional, Lu, Fan, additional, and Qu, Jia, additional
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- 2009
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155. The Development of the Refractive Status and Ocular Growth in C57BL/6 Mice
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Zhou, Xiangtian, primary, Shen, Meixiao, additional, Xie, Jing, additional, Wang, Jianhua, additional, Jiang, Liqin, additional, Pan, Miaozhen, additional, Qu, Jia, additional, and Lu, Fan, additional
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- 2008
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156. Mitochondrial variants may influence the phenotypic manifestation of Leber's hereditary optic neuropathy-associated ND4 G11778A mutation
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Cai, Wanshi, primary, Fu, Qun, additional, Zhou, Xiangtian, additional, Qu, Jia, additional, Tong, Yi, additional, and Guan, Min-Xin, additional
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- 2008
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157. Involvement of PI3K/Akt Signaling Pathway in Hepatocyte Growth Factor–Induced Migration of Uveal Melanoma Cells
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Ye, Mao, primary, Hu, Danning, additional, Tu, Lili, additional, Zhou, Xiangtian, additional, Lu, Fan, additional, Wen, Bin, additional, Wu, Wencan, additional, Lin, Yi, additional, Zhou, Zhonglou, additional, and Qu, Jia, additional
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- 2008
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158. Development of the human dorsal nucleus of the vagus
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Cheng, Gang, primary, Zhu, Hua, additional, Zhou, Xiangtian, additional, Qu, Jia, additional, Ashwell, K.W.S., additional, and Paxinos, G., additional
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- 2008
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159. The coexistence of mitochondrial ND6 T14484C and 12S rRNA A1555G mutations in a Chinese family with Leber’s hereditary optic neuropathy and hearing loss
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Wei, Qi-Ping, primary, Zhou, Xiangtian, additional, Yang, Li, additional, Sun, Yan-Hong, additional, Zhou, Jian, additional, Li, Guang, additional, Jiang, Robert, additional, Lu, Fan, additional, Qu, Jia, additional, and Guan, Min-Xin, additional
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- 2007
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160. The mitochondrial tRNAGlu A14693G mutation may influence the phenotypic manifestation of ND1 G3460A mutation in a Chinese family with Leber’s hereditary optic neuropathy
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Tong, Yi, primary, Mao, Yijian, additional, Zhou, Xiangtian, additional, Yang, Li, additional, Zhang, Juanjuan, additional, Cai, Wanshi, additional, Zhao, Fuxing, additional, Wang, Xinjian, additional, Lu, Fan, additional, Qu, Jia, additional, and Guan, Min-Xin, additional
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- 2007
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161. Cosegregation of the ND4 G11696A mutation with the LHON-associated ND4 G11778A mutation in a four generation Chinese family
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Qu, Jia, primary, Li, Ronghua, additional, Zhou, Xiangtian, additional, Tong, Yi, additional, Yang, Li, additional, Chen, Jie, additional, Zhao, Fuxing, additional, Lu, Chunjie, additional, Qian, Yaping, additional, Lu, Fan, additional, and Guan, Min-Xin, additional
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- 2007
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162. Feasibility of Two-Dimensional Gel Electrophoresis Used for Proteomic Analysis of Human Scleral Fibroblasts
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Lu, Fan, primary, Zhou, Xiangtian, additional, Xie, Ruozhong, additional, Wu, Yaming, additional, Hu, Yongwu, additional, Zhang, Lihua, additional, Li, He, additional, Mao, Xinjie, additional, Hu, Dannin, additional, and Qu, Jia, additional
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- 2007
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163. The mitochondrial tRNAThr A15951G mutation may influence the phenotypic expression of the LHON-associated ND4 G11778A mutation in a Chinese family
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Li, Ronghua, primary, Qu, Jia, additional, Zhou, Xiangtian, additional, Tong, Yi, additional, Hu, Yongwu, additional, Qian, Yaping, additional, Lu, Fan, additional, Mo, Jun Qin, additional, West, Constance E., additional, and Guan, Min-Xin, additional
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- 2006
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164. The Novel A4435G Mutation in the Mitochondrial tRNAMetMay Modulate the Phenotypic Expression of the LHON-Associated ND4 G11778A Mutation
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Qu, Jia, primary, Li, Ronghua, additional, Zhou, Xiangtian, additional, Tong, Yi, additional, Lu, Fan, additional, Qian, Yaping, additional, Hu, Yongwu, additional, Mo, Jun Qin, additional, West, Constance E., additional, and Guan, Min-Xin, additional
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- 2006
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165. Leber’s hereditary optic neuropathy is associated with the mitochondrial ND4 G11696A mutation in five Chinese families
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Zhou, Xiangtian, primary, Wei, Qiping, additional, Yang, Li, additional, Tong, Yi, additional, Zhao, Fuxin, additional, Lu, Chunjie, additional, Qian, Yaping, additional, Sun, Yanghong, additional, Lu, Fan, additional, Qu, Jia, additional, and Guan, Min-Xin, additional
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- 2006
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166. The Presence of m1 to m5 Receptors in Human Sclera: Evidence of the Sclera as a Potential Site of Action for Muscarinic Receptor Antagonists
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Qu, Jia, primary, Zhou, Xiangtian, additional, Xie, Ruozhong, additional, Zhang, Lihua, additional, Hu, Danning, additional, Li, He, additional, and Lu, Fan, additional
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- 2006
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167. Clinical evaluation and mitochondrial DNA sequence analysis in three Chinese families with Leber’s hereditary optic neuropathy
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Qian, Yaping, primary, Zhou, Xiangtian, additional, Hu, Yongwu, additional, Tong, Yi, additional, Li, Ronghua, additional, Lu, Fan, additional, Yang, Huanming, additional, Mo, Jun Qin, additional, Qu, Jia, additional, and Guan, Min-Xin, additional
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- 2005
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168. Only male matrilineal relatives with Leber’s hereditary optic neuropathy in a large Chinese family carrying the mitochondrial DNA G11778A mutation
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Qu, Jia, primary, Li, Ronghua, additional, Tong, Yi, additional, Hu, Yongwu, additional, Zhou, Xiangtian, additional, Qian, Yaping, additional, Lu, Fan, additional, and Guan, Min-Xin, additional
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- 2005
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169. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error
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Fan, Qiao, Verhoeven, Virginie J M, Wojciechowski, Robert, Barathi, Veluchamy A, Hysi, Pirro G, Guggenheim, Jeremy A, Höhn, René, Vitart, Veronique, Khawaja, Anthony P, Yamashiro, Kenji, Hosseini, S Mohsen, Lehtimäki, Terho, Lu, Yi, Haller, Toomas, Xie, Jing, Delcourt, Cécile, Pirastu, Mario, Wedenoja, Juho, Gharahkhani, Puya, Venturini, Cristina, Miyake, Masahiro, Hewitt, Alex W, Guo, Xiaobo, Mazur, Johanna, Huffman, Jenifer E, Williams, Katie M, Polasek, Ozren, Campbell, Harry, Rudan, Igor, Vatavuk, Zoran, Wilson, James F, Joshi, Peter K, McMahon, George, St Pourcain, Beate, Evans, David M, Simpson, Claire L, Schwantes-An, Tae-Hwi, Igo, Robert P, Mirshahi, Alireza, Cougnard-Gregoire, Audrey, Bellenguez, Céline, Blettner, Maria, Raitakari, Olli, Kähönen, Mika, Seppala, Ilkka, Zeller, Tanja, Meitinger, Thomas, Ried, Janina S, Gieger, Christian, Portas, Laura, Van Leeuwen, Elisabeth M, Amin, Najaf, Uitterlinden, André G, Rivadeneira, Fernando, Hofman, Albert, Vingerling, Johannes R, Wang, Ya Xing, Wang, Xu, Tai-Hui Boh, Eileen, Ikram, M Kamran, Sabanayagam, Charumathi, Gupta, Preeti, Tan, Vincent, Zhou, Lei, Ho, Candice E H, Lim, Wan'e, Beuerman, Roger W, Siantar, Rosalynn, Tai, E-Shyong, Vithana, Eranga, Mihailov, Evelin, Khor, Chiea-Chuen, Hayward, Caroline, Luben, Robert N, Foster, Paul J, Klein, Barbara E K, Klein, Ronald, Wong, Hoi-Suen, Mitchell, Paul, Metspalu, Andres, Aung, Tin, Young, Terri L, He, Mingguang, Pärssinen, Olavi, Van Duijn, Cornelia M, Jin Wang, Jie, Williams, Cathy, Jonas, Jost B, Teo, Yik-Ying, Mackey, David A, Oexle, Konrad, Yoshimura, Nagahisa, Paterson, Andrew D, Pfeiffer, Norbert, Wong, Tien-Yin, Baird, Paul N, Stambolian, Dwight, Wilson, Joan E Bailey, Cheng, Ching-Yu, Hammond, Christopher J, Klaver, Caroline C W, Saw, Seang-Mei, Rahi, Jugnoo S, Korobelnik, Jean-François, Kemp, John P, Timpson, Nicholas J, Smith, George Davey, Craig, Jamie E, Burdon, Kathryn P, Fogarty, Rhys D, Iyengar, Sudha K, Chew, Emily, Janmahasatian, Sarayut, Martin, Nicholas G, MacGregor, Stuart, Xu, Liang, Schache, Maria, Nangia, Vinay, Panda-Jonas, Songhomitra, Wright, Alan F, Fondran, Jeremy R, Lass, Jonathan H, Feng, Sheng, Zhao, Jing Hua, Khaw, Kay-Tee, Wareham, Nick J, Rantanen, Taina, Kaprio, Jaakko, Pang, Chi Pui, Chen, Li Jia, Tam, Pancy O, Jhanji, Vishal, Young, Alvin L, Döring, Angela, Raffel, Leslie J, Cotch, Mary-Frances, Li, Xiaohui, Yip, Shea Ping, Yap, Maurice K H, Biino, Ginevra, Vaccargiu, Simona, Fossarello, Maurizio, Fleck, Brian, Yazar, Seyhan, Tideman, Jan Willem L, Tedja, Milly, Deangelis, Margaret M, Morrison, Margaux, Farrer, Lindsay, Zhou, Xiangtian, Chen, Wei, Mizuki, Nobuhisa, Meguro, Akira, and Mäkelä, Kari Matti
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10. No inequality ,610 Medicine & health ,3. Good health - Abstract
Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P
170. Sustained abnormality with recovery of COVID-19 convalescents: a 2-year follow-up study.
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Lin, Hao, Liu, Xueyuan, Sun, Heqiang, Zhang, Jie, Dong, Shaobo, Liu, Maoshun, Li, Lei, Tian, Jinmin, Guo, Yaxin, Gan, Jinxian, Chen, Zhangfu, Wang, Xin, Lin, Ying, Zhang, Danni, Liu, Yaning, Zhang, Xiaoshan, Liu, Peipei, Xu, Ke, Zhou, Xiangtian, and Liang, Hao
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COVID-19 , *HUMAN abnormalities - Abstract
[Display omitted] [ABSTRACT FROM AUTHOR]
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- 2022
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171. The mitochondrial tRNAGlu A14693G mutation may influence the phenotypic manifestation of ND1 G3460A mutation in a Chinese family with Leber’s hereditary optic neuropathy
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Tong, Yi, Mao, Yijian, Zhou, Xiangtian, Yang, Li, Zhang, Juanjuan, Cai, Wanshi, Zhao, Fuxing, Wang, Xinjian, Lu, Fan, Qu, Jia, and Guan, Min-Xin
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TRANSFER RNA , *GENETIC mutation , *NUCLEIC acids , *MITOCHONDRIA - Abstract
Abstract: We report here the clinical, genetic, and molecular characterization of one Han Chinese family with maternally transmitted Leber’s hereditary optic neuropathy (LHON). Three of seven matrilineal relatives in this family exhibited the variable degree of central vision loss at the age of 12, 14, and 16 years old, respectively. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the ND1 G3460A mutation and 47 other variants, belonging to the Asian haplogroup M7b2. The G3460A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the homoplasmic A14693G mutation is of special interest as it was implicated to be associated with other mitochondrial disorders. This mutation is located at the TψC-loop, at conventional position 54 of tRNAGlu. The uridine at this position (U54), which is highly conserved from bacteria to human mitochondria, has been implicated to be important for tRNA structure and function. Thus, the A14693G mutation may alter the tertiary structure of this tRNA, cause a failure in this tRNA metabolism, thereby worsening the mitochondrial dysfunction associated with the primary G3460A mutation. Therefore, the tRNAGlu A14693G mutation may have a potential modifier role in the phenotypic manifestation of the primary LHON-associated G3460A mutation in this Chinese family. [Copyright &y& Elsevier]
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- 2007
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172. Leber’s hereditary optic neuropathy is associated with the mitochondrial ND6 T14484C mutation in three Chinese families
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Sun, Yan-Hong, Wei, Qi-Ping, Zhou, Xiangtian, Qian, Yaping, Zhou, Jian, Lu, Fan, Qu, Jia, and Guan, Min-Xin
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NEUROPATHY , *VISION disorders , *MITOCHONDRIAL DNA , *NUCLEIC acids , *GENES , *GENETICS - Abstract
Abstract: We report here the clinical, genetic, and molecular characterization of three Chinese families with maternally transmitted Leber’s hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. In the affected matrilineal relatives, the loss of central vision is bilateral, the fellow eye becoming affected either simultaneously (45%) or sequentially (55%). The penetrances of vision loss in these pedigrees were 27%, 50%, and 60%, respectively. The age-at-onset of vision loss in these families was 14, 19, and 24 years, respectively. Furthermore, the ratios between affected male and female matrilineal relatives were 1:1, 1:1.2, and 1:2, respectively. Mutational analysis of mitochondrial DNA revealed the presence of homoplasmic ND6 T14484C mutation, which has been associated with LHON. The incomplete penetrance and phenotypic variability implicate the involvement of nuclear modifier gene(s), environmental factor(s) or mitochondrial haplotype(s) in the phenotypic expression of the LHON-associated T14484C mutation in these Chinese pedigrees. [Copyright &y& Elsevier]
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- 2006
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173. The mitochondrial tRNAThr A15951G mutation may influence the phenotypic expression of the LHON-associated ND4 G11778A mutation in a Chinese family
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Li, Ronghua, Qu, Jia, Zhou, Xiangtian, Tong, Yi, Hu, Yongwu, Qian, Yaping, Lu, Fan, Mo, Jun Qin, West, Constance E., and Guan, Min-Xin
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NEUROPATHY , *MITOCHONDRIAL DNA , *NUCLEIC acids , *GENES , *BLINDNESS - Abstract
Abstract: We report here the characterization of a three-generation Han Chinese family with Leber''s hereditary optic neuropathy (LHON). This Chinese family exhibited high penetrance and expressivity of visual impairment. The average age-of-onset was 19 years in this family. All male and 33% female matrilineal relatives in this Chinese family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the ND4 G11778A mutation and 40 other variants, belonging to the Asian haplogroup D4. The G11778A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the homoplasmic A15951G mutation is of special interest as it is located adjacent to 3′ end, at conventional position 71 of tRNAThr. The adenine (A71) at this position of tRNAThr, highly conserved from bacteria to human mitochondria, has been implicated to be important for tRNA identity and pre-tRNA processing. In fact, the significant reduction of the steady-state levels in tRNAThr was observed in cells carrying both the A15951G and G11778A mutations but not cells carrying only G11778A mutation. Thus, the A15951G mutation most probably leads to a failure in mitochondrial tRNA metabolism, worsening the mitochondrial dysfunction associated with the primary G11778A mutation. These imply that the tRNAThr A15951G mutation may have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family. [Copyright &y& Elsevier]
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- 2006
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174. Conjunctival MUC5AC+ goblet cell index: relationship with corneal nerves and dry eye.
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Chao, Cecilia, Golebiowski, Blanka, Stapleton, Fiona, Zhou, Xiangtian, Chen, Shihao, and Madigan, Michele C.
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DRY eye syndromes , *CORNEA diseases , *MUCIN genetics , *EYE drops , *EXFOLIATIVE cytology - Abstract
Purpose: To evaluate the relative proportion of conjunctival MUC5AC+ and MUC5AC− goblet cells in a post-LASIK population and their association with dry eye indicators and corneal nerve morphology using a MUC5AC+ Goblet Cell Index.Methods: Twenty subjects who had undergone LASIK > 12 months previously and 20 age-matched controls were recruited. Dry eye symptoms, tear breakup time, osmolarity, meniscus area and corneal nerve morphology were examined. Conjunctival impression cytology samples were collected from inferior-temporal bulbar conjunctiva using Millicell® inserts. Total goblet cell density was determined from positive cytokeratin-7 (CK7) immunolabelling; MUC5AC+ goblet cell density was determined from both CK7+- and MUC5AC+-immunolabelled cells. The ratio of MUC5AC+ to total density was defined as the “MUC5AC+ Goblet Cell Index”. Differences in variables between groups and the associations between goblet cell variables and clinical assessments were examined.Results: No significant differences in the total and MUC5AC+ goblet cell density and tear film parameters were found between groups, although greater ocular discomfort was reported in the post-LASIK group (P = 0.02). A higher MUC5AC+ Index was associated with worse/greater dry eye symptoms (ρ = 0.55, P = 0.01) and higher nerve tortuosity (ρ = 0.57, P = 0.01) in the post-LASIK group; lower nerve density and thickness was found in controls (ρ > −0.45, P < 0.05), but not associated with tear film parameters.Conclusions: The MUC5AC+ Goblet Cell Index provides an indicator of mucin secretion for assessing the goblet cell function in dry eye. In the post-LASIK participants, we found an increased MUC5AC+ Index associated with worse dry eye symptoms and adverse changes in corneal nerve morphology. [ABSTRACT FROM AUTHOR]
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- 2018
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175. Choroidal blood perfusion could predict the sensitivity of myopia formation in Guinea pigs.
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Yang, Yaozhen, Chen, Mengxi, Yao, Xinyuan, Wang, Jiao, Shi, Jiajia, Wang, Yuanyuan, Tian, Jinmin, Zhou, Xiangtian, Qu, Jia, and Zhang, Sen
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GUINEA pigs , *MYOPIA , *VISUAL accommodation , *CHOROID , *OPTICAL coherence tomography - Abstract
In this study, we explored the predictive role of choroidal blood perfusion (ChBP) and choroidal thickness (ChT) on the development of myopia in guinea pigs. Optical Coherence Tomography Angiography (OCTA) was used to assess the baseline choroidal blood perfusion (ChBP) and choroidal thickness (ChT) in 4-week-old guinea pigs. Refraction and axial length (AL) were measured at baseline. Myopia was induced for one week using form-deprivation (FD) or negative lenses followed by measurements of refraction, axial length and choroidal parameters (ChT and ChBP). The correlations were evaluated between the baseline choroidal values and the magnitude of myopia induced, along with the magnitude of changes in ChT and ChBP after myopia induction. There was a significant correlation between the baseline choroidal parameters and ocular refraction. Myopia induction led to choroidal thinning and less ChBP as well as longer eyes. On the other hand, following exposure to the same non-obstructed visual induction period, the myopic shift was less, and it was associated with thicker choroids and more ChBP at baseline. One week of myopia induction also resulted in thinner choroids and less ChBP, and these declines also correlated with their baseline values. In conclusion, the present study shows that the changes in the baseline choroidal ChT and ChBP parameters are proportional to the magnitude of myopia development and axial elongation in guinea pigs. These significant correlations between baseline ChBP and ChT and myopia development suggest that they may be a viable predictor of this process in guinea pigs. • This study evaluates the possibility of choroidal blood perfusion (ChBP) as a predictor of myopia development in guinea pigs. • A tenable explanation is provided for why assessment of choroidal thickness (ChT) is indicative of myopia development. • Excellent correlations exist between baseline ChT and ChBP and magnitudes of myopia induction. [ABSTRACT FROM AUTHOR]
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- 2023
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176. Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation.
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Ye, Rong, Hu, Naijing, Cao, Changchang, Su, Ruibao, Xu, Shihan, Yang, Chen, Zhou, Xiangtian, and Xue, Yuanchao
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RNA splicing , *LOCUS (Genetics) , *RNA-binding proteins , *INTRONS , *GENETIC regulation , *RNA analysis , *ALTERNATIVE RNA splicing - Abstract
RNA-binding proteins (RBPs) bind at different positions of the pre-mRNA molecules to promote or reduce the usage of a particular exon. Seeking to understand the working principle of these positional effects, we develop a capture RIC-seq (CRIC-seq) method to enrich specific RBP-associated in situ proximal RNA-RNA fragments for deep sequencing. We determine hnRNPA1-, SRSF1-, and PTBP1-associated proximal RNA-RNA contacts and regulatory mechanisms in HeLa cells. Unexpectedly, the 3D RNA map analysis shows that PTBP1-associated loops in individual introns preferentially promote cassette exon splicing by accelerating asymmetric intron removal, whereas the loops spanning across cassette exon primarily repress splicing. These "positional rules" can faithfully predict PTBP1-regulated splicing outcomes. We further demonstrate that cancer-related splicing quantitative trait loci can disrupt RNA loops by reducing PTBP1 binding on pre-mRNAs to cause aberrant splicing in tumors. Our study presents a powerful method for exploring the functions of RBP-associated RNA-RNA proximal contacts in gene regulation and disease. [Display omitted] • CRIC-seq maps specific RBP-associated RNA-RNA spatial contacts • Positional rules of PTBP1-associated RNA loops in splicing regulation • PTBP1-associated intronic RNA loops facilitate asymmetrical intron removal • sQTLs disrupt PTBP1-associated RNA loops to promote tumor cell growth Ye et al. have developed a new method, named CRIC-seq, for the global profiling of PTBP1-associated RNA-RNA spatial contacts. The authors unravel the positional mechanisms by which PTBP1-associated RNA loops enhance or repress splicing, demonstrating that cancer-related splicing quantitative trait loci can disrupt PTBP1-associated RNA loops to promote tumor cell growth. [ABSTRACT FROM AUTHOR]
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- 2023
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177. Near work induces myopia in Guinea pigs.
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Fu, Qian, Zhang, Yue, Chen, Linji, Dong, Mengmeng, Tang, Wenyu, Chen, Si, Qu, Jia, Zhou, Xiangtian, and Zhi, Zhina
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GUINEA pigs , *MYOPIA , *CHOROID , *OPTICAL coherence tomography - Abstract
The association between near work activities and myopia has not been clearly established. This study establishes a model for near work myopia (NWM) induced by short viewing distance in guinea pigs with a carefully controlled visual environment, and evaluates the effect of viewing distance in myopia development. Pigmented guinea pigs (3 weeks old) were randomly assigned to 3 groups: near work (NW)-, form-deprivation (FD)-, and -4D hyperopic-defocus (HD)-induced myopia. Animals in NW groups were kept in cylindrical cages with vertical square-wave gratings, providing short- (S, d = 18 cm), middle- (M, d = 44 cm), and long- (L, d = 88 cm) mean viewing distances, all at the same illuminance, during daily treatment for 14 days. Biometric parameters, including refraction, anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL), were measured at the beginning and end of 14 days' treatment. Choroidal thickness (ChT) and choroidal blood perfusion (ChBP) were measured by optical coherence tomography (OCT) and OCT-angiography (OCTA), respectively, at the end of treatment. Refraction was shifted towards myopia in the S-cage group, compared with the M- and L-cage groups; refractions in the L-, M- and S-cage groups were 5.19 ± 0.65 D, 4.30 ± 0.64 D, and 0.53 ± 0.61 D, respectively (p < 0.001). VCD and AL in the S-cage group increased in parallel with the myopic shift (L vs M vs S: VCD: 3.15 ± 0.02 mm vs 3.17 ± 0.02 mm vs 3.26 ± 0.02 mm, p < 0.001; AL: 7.99 ± 0.03 mm vs 8.03 ± 0.03 mm vs 8.15 ± 0.02 mm, p = 0.001). In FD and HD eyes, changes similar to those in the S-cage group (near-work group, NW) were seen in refraction (NW vs FD vs HD: 5.36 ± 0.82 D vs −5.78 ± 0.44 D vs −4.96 ± 0.54 D, p = 0.734), ACD, LT, VCD and AL. Also, ChT and ChBP were significantly less in the S-cage group than in the M- and L-cage groups after 14 days' treatment (L vs M vs S: ChT: 74.84 ± 3.27 vs 76.07 ± 3.49 vs 61.95 ± 3.31, P = 0.002; ChBP: 48.32 ± 2.23 vs 48.66 ± 2.30 vs 38.14 ± 2.06, p = 0.002). Rearing in S-cages induced myopia in guinea pigs and correspondingly decreased ChBP and ChT. The present study provides objective evidence that short viewing distance could be a risk factor for myopia, and describes a useful model for studying the underlying mechanisms. • This study establishes a novel near work myopia animal model in guinea pigs. • Short viewing distance induces myopia in guinea pigs. • Myopia induced by short viewing distance is similar to that induced by form deprivation/defocus. • Short viewing distance decreases choroidal blood perfusion and choroidal thickness. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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178. Effects of muscarinic receptor modulators on ocular biometry of guinea pigs.
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Fang, Fang, Huang, Furong, Xie, Ruozhong, Li, Cheng, Liu, Yin, Zhu, Ying, Qu, Jia, and Zhou, Xiangtian
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MUSCARINIC receptors , *VISUAL accommodation , *PILOCARPINE , *REFRACTIVE errors , *GUINEA pigs as laboratory animals - Abstract
Purpose This study investigated whether pilocarpine and cyclopentolate induce changes in ocular biometry of guinea pigs, in order to understand if guinea pigs have a similar response to these two agents as humans do. Methods Under general anaesthesia, refraction, axial components and surface curvature in various optical interfaces of the eye were measured in 10 guinea pigs (age of 2 weeks) at baseline (0 min) and different time points (5, 10, 20, 30, 60, 90 min) after topical administration of pilocarpine or cyclopentolate. The interval between the two drug treatments for the same animals was at least 24 h. Results Eyes treated with pilocarpine developed approximately 6D myopia ( p < 0.001 from 0 to 90 min) with a decrease in anterior lens radius of curvature ( ALRC) ( p < 0.001 from 0 to 90 min, repeated measures anova). This myopic shift was moderately correlated to the decreased ALRC ( r2 = 0.48, p < 0.001). Furthermore, a small but significant increase in the VCD ( p < 0.001 from 0 to 30 min, repeated measures anova) with an unchanged AL ( p = 0.85 from 0 to 90 min, repeated measures anova) after the drug treatment suggested a transient and mild forward movement of the lens. Cyclopentolate dilated the pupil in all eyes ( p < 0.001 from 0 to 90 min, repeated measures anova) but did not change other ocular parameters. Conclusions The muscarinic agonist, pilocarpine induced a myopic shift mainly due to a decrease in ALRC, suggesting that guinea pigs have an accommodative mechanism similar to that in humans. The minimal changes produced by cyclopentolate could be due to the use of general anaesthesia, which may have reduced the susceptibility of the eye to topical cyclopentolate in the induction of cycloplegia. [ABSTRACT FROM AUTHOR]
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- 2015
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179. Form-deprivation myopia downregulates calcium levels in retinal horizontal cells in mice.
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Li, Qihang, Zhu, He, Fan, Miaomiao, Sun, Jing, Reinach, Peter S., Wang, Yuhan, Qu, Jia, Zhou, Xiangtian, and Zhao, Fuxin
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MYOPIA , *CALBINDIN , *CALCIUM , *MICE , *RETINAL imaging , *LABORATORY mice - Abstract
The process of eye axis lengthening in myopic eyes is regulated by multiple mechanisms in the retina, and horizontal cells (HCs) are an essential interneuron in the visual regulatory system. Wherein intracellular Ca2+ plays an important role in the events involved in the regulatory role of HCs in the retinal neural network. It is unknown if intracellular Ca2+ regulation in HCs mediates changes in the retinal neural network during myopia progression. We describe here a novel calcium fluorescence indicator system that monitors HCs' intracellular Ca2+ levels during form-deprivation myopia (FDM) in mice. AAV injection of GCaMP6s, as a protein calcium sensor, into a Gja10-Cre mouse monitored the changes in Ca2+signaling in HC that accompany FDM progression in mice. An alternative Gja10-Cre/Ai96-GCaMP6s mouse model was created by cross mating Gja10-Cre with Ai96 mice. Immunofluorescence imaging and live imaging of the retinal cells verified the identity of these animal models. Changes in retinal horizontal cellular Ca2+ levels were resolved during FDM development. The numbers of GCaMP6s and the proportion of HCs were tracked based on profiling changes in GCaMP6s+calbindin+/calbindin+ coimmunostaining patterns. They significantly decreased more after either two days (P < 0.01) or two weeks (P < 0.001) in form deprived eyes than in the untreated fellow eyes. These decreases in their proportion reached significance only in the retinal central region rather than also in the retinal periphery. A novel approach employing a GCaMP6s mouse model was developed that may ultimately clarify if HCs mediate Ca2+ signals that contribute to controlling FDM progression in mice. The results indicate so far that FDM progression is associated with declines in HC Ca2+ signaling activity. • FDM downregulates calcium level in horizontal cells either two days or two weeks. • Downregulation of Ca2+ in horizontal cells is region-specific only in the retinal center. • GCaMP6 mouse model can clarify HCs mediate Ca2+ signals that contribute to controlling FDM. [ABSTRACT FROM AUTHOR]
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- 2022
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180. Interactions of chromatic and lens-induced defocus during visual control of eye growth in guinea pigs (Cavia porcellus)
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Jiang, Liqin, Zhang, Sen, Schaeffel, Frank, Xiong, Shibo, Zheng, Yibo, Zhou, Xiangtian, Lu, Fan, and Qu, Jia
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- 2014
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181. Exome sequencing reveals CCDC111 mutation associated with high myopia.
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Zhao, Fuxin, Wu, Jinyu, Xue, Anquan, Su, Yanfeng, Wang, Xiaojing, Lu, Xianmin, Zhou, Zhonglou, Qu, Jia, and Zhou, Xiangtian
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MYOPIA , *REFRACTIVE errors , *EYE diseases , *CATARACT , *GLAUCOMA , *RETINAL degeneration - Abstract
Myopia is a refractive error of the eye that is prevalent worldwide. The most extreme form, high myopia, is usually associated with other ocular disorders such as retinal detachment, macular degeneration, cataract, and glaucoma, and is one of leading causes of blindness. The etiology is complex and has not been fully elucidated. In this study, we identified a novel missense variant of the CCDC111 gene (NM_152683.2: c.265T > G; p.Y89D) in a high myopia family by exome sequencing. The variant was identified in 4 patients from an additional 270 sporadic high myopia patients, but not found in 270 controls. The amino acid is highly conserved across species, and variants giving rise to amino acid substitutions are predicted to be functionally damaging. The CCDC111 gene was ubiquitously expressed in primary cell cultures from human eye tissue, including corneal epithelial cells, choroidal melanoma cells, scleral fibroblasts, retinal epithelial cells, retinal Müller cells, and lens capsule epithelial cells. In summary, our results suggested that the CCDC111 may be a susceptibility gene for high myopia. [ABSTRACT FROM AUTHOR]
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- 2013
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182. Self-complementary AAV5 vector facilitates quicker transgene expression in photoreceptor and retinal pigment epithelial cells of normal mouse
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Kong, Fansheng, Li, Wensheng, Li, Xia, Zheng, Qinxiang, Dai, Xufeng, Zhou, Xiangtian, Boye, Sanford L., Hauswirth, William W., Qu, Jia, and Pang, Ji-jing
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PHOTORECEPTORS , *RHODOPSIN , *EPITHELIAL cells , *TRANSGENE expression , *LABORATORY mice , *GENETIC transduction , *RECOMBINANT viruses , *GREEN fluorescent protein - Abstract
Abstract: To clarify whether transduction efficiency and cell type specificity of self-complementary (sc) AAV5 vectors are similar to those of standard, single-stranded AAV5 vectors in normal retina, one micro liter of scAAV5-smCBA-GFP vector (1×1012 genome-containing particles/ml) and AAV5-smCBA-GFP vector (1×1012 genome-containing particles/ml) were subretinally or intravitreally (in both cases through the cornea) injected into the right and left eyes of adult C57BL/6J mice, respectively. On post-injection day (PID) 1, 2, 5, 7, 10, 14, 21, 28 and 35, eyes were enucleated; retinal pigment epithelium (RPE) wholemounts, neuroretinal wholemounts and eyecup sections were prepared to evaluate green fluorescent protein (GFP) expression by fluorescent microscopy. GFP expression following trans-cornea subretinal injection of scAAV5-smCBA-GFP vector was first detected in RPE wholemounts around PID 1 and in neuroretinal wholemounts between PID 2 and 5; GFP expression peaked and stabilized between PID 10–14 in RPE wholemounts and between P14 and P21 in neuroretinal wholemounts with strong, homogeneous green fluorescence covering the entire wholemounts. The frozen sections supported the following findings from the wholemounts: GFP expression appeared first in RPE around PID 1–2 and soon spread to photoreceptors (PR) cells; by PID 7, moderate GFP expression was found mainly in PR and RPE layers; between PID 14 and 21, strong and homogenous GFP expression was observed in RPE and PR cells. GFP expression following subretinal injection of AAV5-smCBA-GFP was first detected in RPE wholemounts around PID 5–7 and in neuroretinal wholemounts around PID 7–10; ssAAV5-mediated GFP expression peaked at PID 21 in RPE wholemounts and around PID 28 in neuroretinal wholemounts; sections from AAV5 treated eyes also supported findings obtained from wholemounts: GFP expression was first detected in RPE and then spread to the PR cells. Peak GFP expression in RPE mediated by scAAV5 was similar to that mediated by AAV5. However, peak GFP expression mediated by scAAV5 in PR cells was stronger than that mediated by AAV5. No GFP fluorescence was detected in any retinal cells (RPE wholemounts, neuroretinal wholemounts and retinal sections) after trans-cornea intravitreal delivery of either scAAV5-GFP or AAV5-GFP. Neither scAAV5 nor AAV5 can transduce retinal cells following trans-cornea intravitreal injection. The scAAV5 vector used in this study directs an earlier onset of transgene expression than the matched AAV5 vector, and has stronger transgene expression in PR cells following subretinal injection. Our data confirm the previous reports that scAAV vectors have an earlier onset than the standard, single strand AAV vectors (). scAAV5 vectors may be more useful than standard, single-stranded AAV vector when addressing certain RPE and/or PR cell-related models of retinal dystrophy, particularly for mouse models of human retinitis pigmentosa that require rapid and robust transgene expression to prevent early degeneration in PR cells. [Copyright &y& Elsevier]
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- 2010
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183. Declines in PDE4B activity promote myopia progression through downregulation of scleral collagen expression.
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Zhao, Fuxin, Zhou, Hui, Chen, Wei, Zhao, Chenchen, Zheng, Yangyang, Tao, Yijin, Pan, Miaozhen, Reinach, Peter S., Zhu, Jiadi, An, Jianhong, Lu, Runxia, Chen, Jiang-fan, Tang, Huifang, Zeng, Changqing, Qu, Jia, and Zhou, Xiangtian
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MYOPIA , *CYCLIC adenylic acid , *ADENOSINE monophosphate , *GENE expression , *COLLAGEN , *CELLULAR signal transduction , *REFRACTIVE errors - Abstract
Myopia is the most common cause of a visual refractive error worldwide. Cyclic adenosine monophosphate (cAMP)-linked signaling pathways contribute to the regulation of myopia development, and increases in cAMP accumulation promote myopia progression. To pinpoint the underlying mechanisms by which cAMP modulates myopia progression, we performed scleral transcriptome sequencing analysis in form-deprived mice, a well-established model of myopia development. Form deprivation significantly inhibited the expression levels of genes in the cAMP catabolic pathway. Quantitative real-time polymerase chain reaction analysis validated that the gene expression level of phosphodiesterase 4B (PDE4B), a cAMP hydrolase, was downregulated in form-deprived mouse eyes. Under visually unobstructed conditions, loss of PDE4B function in Pde4b -knockout mice increased the myopic shift in refraction, −3.661 ± 1.071 diopters, more than that in the Pde4b -wildtype littermates (P < 0.05). This suggests that downregulation and inhibition of PDE4B gives rise to myopia. In guinea pigs, subconjunctival injection of rolipram, a selective inhibitor of PDE4, led to myopia in normal eyes, and it also enhanced form-deprivation myopia (FDM). Subconjunctival injection of dibutyryl-cyclic adenosine monophosphate, a cAMP analog, induced only a myopic shift in the normal visually unobstructed eyes, but it did not enhance FDM. As myopia developed, axial elongation occurred during scleral remodeling that was correlated with changes in collagen fibril thickness and distribution. The median collagen fibril diameter in the FDM + rolipram group, 55.09 ± 1.83 nm, was thinner than in the FDM + vehicle group, 59.33 ± 2.06 nm (P = 0.011). Thus, inhibition of PDE4 activity with rolipram thinned the collagen fibril diameter relative to the vehicle treatment in form-deprived eyes. Rolipram also inhibited increases in collagen synthesis induced by TGF-β2 in cultured human scleral fibroblasts. The current results further support a role for PDE enzymes such as PDE4B in the regulation of normal refractive development and myopia because either loss or inhibition of PDE4B function increased myopia and FDM development through declines in the scleral collagen fibril diameter. ● Pde4b mRNA expression was downregulated in form-deprived eyes of mice ● Pde4b knockout leads to a refraction shift towards myopia in mice ● Inhibition of PDE4B by rolipram leads to myopia in normal guinea pig eyes and enhances form deprivation myopia ● Inhibition of PDE4B with rolipram thins the scleral collagen fibril diameter in form-deprived eyes ● PDE4B is an important gene involved in modulating myopia progression through suppression of scleral collagen [ABSTRACT FROM AUTHOR]
- Published
- 2021
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184. Author Correction: A role of color vision in emmetropization in C57BL/6J mice.
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Yang, Jinglei, Yang, Li, Chen, Rongfang, Zhu, Yun, Wang, Siyao, Hou, Xueqin, Wei, Bei, Wang, Qiongsi, Liu, Yue, Qu, Jia, and Zhou, Xiangtian
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COLOR vision , *VISUAL perception - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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185. PPARγ modulates refractive development and form deprivation myopia in Guinea pigs.
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Pan, Miaozhen, Guan, Zhenqi, Reinach, Peter S., Kang, Lin, Cao, Yuqing, Zhou, Dengke, Srinivasalu, Nethrajeith, Zhao, Fei, Qu, Jia, and Zhou, Xiangtian
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GUINEA pigs , *PEROXISOME proliferator-activated receptors , *WESTERN immunoblotting , *MYOPIA , *HYPOXIA-inducible factors - Abstract
Form deprivation myopia (FDM) is characterized by loss of choroidal thickness (ChT), reduced choroidal blood perfusion (ChBP), and consequently scleral hypoxia. In some tissues, changes in levels of peroxisome proliferator-activated receptor γ (PPARγ) expression modulate hypoxia-induced pathological responses. We determined if PPARγ modulates FDM through changes in ChT, ChBP, scleral hypoxia-inducible transcription factor (HIF-1α) that in turn regulate scleral collagen type 1 (COL1) expression levels in guinea pigs. Myopia was induced by occluding one eye, while the fellow eye served as control. They received daily peribulbar injections of either the PPARγ antagonist GW9662, or the GW1929 agonist, with or without ocular occlusion for 4 weeks. Ocular refraction and biometric parameters were estimated at baseline, 2 and 4 weeks post-treatment. ChT and ChBP were measured at the 2- and 4-week time points. Western blot analysis determined the expression levels of scleral HIF-1α and COL1. GW9662 induced a myopic shift in unoccluded eyes. Conversely, GW1929 inhibited FDM progression without affecting the refraction in unoccluded eyes. GW9662 reduced both ChT and ChBP in unoccluded eyes, while GW1929 inhibited their declines in occluded eyes. Scleral HIF-1α expression rose in GW9662-treated unoccluded eyes whereas GW1929 reduced HIF-1α upregulation in occluded eyes. GW9662 downregulated scleral COL1 expression in unoccluded eyes, while GW1929 reduced their decreases in occluded eyes. Therefore, PPARγ modulates collagen expression levels and FDM through an inverse relationship between changes in PPARγ and HIF-1α expression levels. • PPARγ agonism and antagonism have opposing effect on refractive development and FDM. • PPARγ agonism reverses FD-induced declines of choroidal thickness and choroidal blood perfusion. • PPARγ agonism reverses FD-induced increases of scleral Hif-1α expression. • PPARγ agonism reverses FD-induced declines scleral collagen type 1 expression. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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186. A role of color vision in emmetropization in C57BL/6J mice.
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Yang, Jinglei, Yang, Li, Chen, Rongfang, Zhu, Yun, Wang, Siyao, Hou, Xueqin, Wei, Bei, Wang, Qiongsi, Liu, Yue, Qu, Jia, and Zhou, Xiangtian
- Subjects
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COLOR vision , *VISUAL accommodation , *ACHROMATISM , *MONOCHROMATIC aberration , *WESTERN immunoblotting , *ANIMAL models in research - Abstract
Spectral composition affects emmetropization in both humans and animal models. Because color vision interacts the effects of chromatic defocus, we developed a method to bypass the effects of longitudinal chromatic aberration by placing a spectral filter behind the optics of the eye, using genetic tools. Newborn C57BL/6J (B6) mice were reared in quasi-monochromatic red (410–510 nm) or blue (585–660 nm) light beginning before eye-opening. Refractive states and ocular dimensions were compared at 4, 6, 8, and 10 weeks with mice reared in normal white light. Cre recombinase-dependent Ai9 reporter mice were crossed with Chx10-Cre to obtain Chx10-Cre;Ai9 mice, expressing red fluorescent protein in retinal Cre-positive cells. Ai9 offsprings, with and without Cre, were reared under a normal visual environment. Refraction and axial components were measured as described above. Expression levels of M and S opsin were quantified by western blotting at 10 weeks. Compared with those reared in white light, B6 mice reared in red light developed relative hyperopia, principally characterized by flattening of corneal curvature. Emmetropization was not affected by blue light, possibly because the reduction in vitreous chamber depth compensated for the increase in corneal curvature. Compared with Cre-negative littermates, the refraction and axial dimensions of Chx10-Cre;Ai9 mice were not significantly different at the follow-up timepoints. M opsin levels were higher in Chx10-Cre;Ai9 mice at 10 weeks while S opsin levels were not different. Red light induced a hyperopic shift in mouse refractive development. Emmetropization was not impacted in mice with perturbed color vision caused by intrinsic red-fluorescent protein, suggesting that color vision may not be necessary in mouse emmetropization when other mechanisms are present. [ABSTRACT FROM AUTHOR]
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- 2020
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187. Short-term choroidal changes as early indicators for future myopic shift in primary school children: results of a 2-year cohort study.
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Wu H, Liu M, Wang Y, Li X, Zhou W, Li H, Xie Z, Wang P, Zhang T, Qu W, Huang J, Zhao Y, Wang J, Zhang S, Qu J, Ye C, and Zhou X
- Abstract
Background: To assess predictive value of short-term choroidal changes for future myopic shift in children., Methods: 577 eyes of 289 primary school children were prospectively followed for 2 years. Cycloplegic refractions at baseline, 1 year and 2 years, and choroidal measurements by optical coherence tomography at baseline and 3 months, were used for analyses. Myopic shift was defined as refraction change of at least -0.50 dioptre/year, at 2 years compared with baseline., Results: 228 participants (455 eyes) completed 2-year follow-up. Approximately 37.6% of 311 initially non-myopic eyes and 73.6% of 144 initially myopic eyes developed a myopic shift. Notably, at 3 months greater reductions were found in initially myopic eyes with myopic shift, than in those without myopic shift-in choroidal thickness (ChT), luminal area (LA), stromal area (SA) and total choroidal area (TCA), but no significant differences in any choroidal parameters were observed between non-myopic eyes, with and without myopic shift. Multivariable analyses showed that in myopic eyes, each percentage increase in ChT, LA, SA and TCA was associated with reduced odds of myopic shift (all p<0.001). Similar associations were observed in non-myopic eyes, with smaller effects than in myopic eyes. Adding a 3-month percentage change of each choroidal parameter to a basic model including age, gender, parental myopia and baseline refraction significantly improved the predictive performance in myopic eyes (area under the receiver operating characteristic curves increasing from 0.650 to approximately 0.800, all p<0.05), but not in non-myopic eyes., Conclusion: Short-term choroidal changes could act as early indicators for future myopic shift in children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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188. Exome-wide association study identifies KDELR3 mutations in extreme myopia.
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Yuan J, Zhuang YY, Liu X, Zhang Y, Li K, Chen ZJ, Li D, Chen H, Liang J, Yao Y, Yu X, Zhuo R, Zhao F, Zhou X, Yu X, Qu J, and Su J
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- Humans, Animals, Male, Female, Fibroblasts metabolism, Exome genetics, Genome-Wide Association Study, Adult, Myopia genetics, Myopia metabolism, Myopia pathology, Sclera metabolism, Sclera pathology, Extracellular Matrix metabolism, Extracellular Matrix genetics, Genetic Predisposition to Disease, Single-Cell Analysis, Case-Control Studies, Child, Young Adult, Zebrafish genetics, Mutation, Exome Sequencing
- Abstract
Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ -10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3's role in EM pathogenesis., (© 2024. The Author(s).)
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- 2024
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189. Choroidal vascular changes in early-stage myopic maculopathy from deep learning choroidal analysis: a hospital-based SS-OCT study.
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Li Y, Li H, Rui X, Wang Y, Zhu S, Huang M, Liang J, Zhu Y, Shi J, Yu L, Huang S, Yang C, Dong M, Gao H, Shen M, Wu H, and Zhou X
- Abstract
Background: The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them., Methods: This study included 1418 highly myopic eyes from 720 participants aged 18 - 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm., Results: DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P < 0.001). An increase in choroidal vascular index (CVI) was observed in all regions, except for the nasal perifoveal (N2) and inferior perifoveal (I2) regions (all P < 0.01). Multivariable logistic regression analysis revealed a negative association between the presence of DCA and increases in choroidal LA and SA (odds ratio ≤ 0.099, P < 0.001). Multivariable linear regression analysis showed that the mean deviation of the visual field test was positively associated with LA and SA at the vertical meridian (B = 1.512, P < 0.001 for LA; B = 1.956, P < 0.001 for SA). Furthermore, the receiver operating characteristic curve analyses showed the optimal ChT to diagnose pathological myopia was 82.4 µm in the N2 region, the LA was 0.076 mm
2 and the SA was 0.049 mm2 , with area under the curves of 0.916, 0.908, and 0.895, respectively., Conclusions: The results of this study indicated that both the presence of DCA and visual function impairment were associated with reductions in choroidal perfusion and stromal components. Moreover, we established threshold values for choroidal parameters in diagnosing pathological myopia, offering valuable references for clinical diagnosis and management., (© 2024. The Author(s).)- Published
- 2024
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190. Efficient pyramid channel attention network for pathological myopia recognition with pretraining-and-finetuning.
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Zhang X, Zhao J, Li Y, Wu H, Zhou X, and Liu J
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- Humans, Myopia, Degenerative, Deep Learning, Fundus Oculi, Image Interpretation, Computer-Assisted methods, Neural Networks, Computer
- Abstract
Pathological myopia (PM) is the leading ocular disease for impaired vision worldwide. Clinically, the characteristics of pathology distribution in PM are global-local on the fundus image, which plays a significant role in assisting clinicians in diagnosing PM. However, most existing deep neural networks focused on designing complex architectures but rarely explored the pathology distribution prior of PM. To tackle this issue, we propose an efficient pyramid channel attention (EPCA) module, which fully leverages the potential of the clinical pathology prior of PM with pyramid pooling and multi-scale context fusion. Then, we construct EPCA-Net for automatic PM recognition based on fundus images by stacking a sequence of EPCA modules. Moreover, motivated by the recent pretraining-and-finetuning paradigm, we attempt to adapt pre-trained natural image models for PM recognition by freezing them and treating the EPCA and other attention modules as adapters. In addition, we construct a PM recognition benchmark termed PM-fundus by collecting fundus images of PM from publicly available datasets. The comprehensive experiments demonstrate the superiority of EPCA-Net over state-of-the-art methods in the PM recognition task. For example, EPCA-Net achieves 97.56% accuracy and outperforms ViT by 2.85% accuracy on the PM-fundus dataset. The results also show that our method based on the pretraining-and-finetuning paradigm achieves competitive performance through comparisons to part of previous methods based on traditional fine-tuning paradigm with fewer tunable parameters, which has the potential to leverage more natural image foundation models to address the PM recognition task in limited medical data regime., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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191. Lactate/lactylation in ocular development and diseases.
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Chai P, Zhao F, Jia R, Zhou X, and Fan X
- Abstract
Lactylation, a post-translational modification (PTM) induced by lactate, has crucial roles in the regulation of transcription, DNA repair, and mitochondrial metabolism. Here, we discuss the role of lactate/lactylation signaling in regulating eye morphogenesis and retinal homeostasis, as well as various ophthalmic disorders, such as myopia, intraocular malignancies, and retinal angiogenesis., Competing Interests: Declaration of interests The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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192. Novel loci for ocular axial length identified through extreme-phenotype genome-wide association study in Chinese populations.
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Han X, Pan S, Liu J, Ding X, Lin X, Wang D, Xie Z, Zeng C, Liu F, He M, Zhou X, Liu T, Luo L, and Liu Y
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- Humans, Male, China epidemiology, Female, Adult, Hyperopia genetics, Genotype, Genetic Loci, Young Adult, Middle Aged, Genetic Predisposition to Disease, East Asian People, Genome-Wide Association Study, Axial Length, Eye pathology, Polymorphism, Single Nucleotide, Asian People genetics, Myopia genetics, Phenotype
- Abstract
Purpose: To investigate genetic loci associated with ocular axial length (AL) in the Chinese population., Methods: A genome-wide association study meta-analysis was conducted in totalling 2644 Chinese individuals from 3 cohorts: the Guangzhou cohort (GZ, 537 high myopes and 151 hyperopes), Wenzhou cohort (334 high myopes and 6 hyperopes) and Guangzhou Twin Eye Study (1051 participants with normally distributed AL). Functional mapping was performed to annotate the significant signals, possible tissues and cell types by integrating available multiomics data. Logistic regression models using AL-associated SNPs were constructed to predict three AL status in GZ., Results: Two novel loci (1q25.2 FAM163A and 7p22.2 SDK1 ) showed genome-wide significant associations with AL, together explaining 29.63% of AL variance in GZ. The two lead SNPs improved the prediction accuracy for AL status, especially for hyperopes. The frequencies of AL decreasing (less myopic) alleles of the two SNPs were lowest in East Asians as compared with other populations (rs17370084: f
EAS =0.03, fEUR =0.24, fAFR =0.05; rs73046501: fEAS =0.06, fEUR =0.07, fAFR =0.20), which was in line with the global distribution of myopia. The cerebral cortex and gamma-aminobutyric acidergic interneurons showed possible functional involvement in myopia development, and the galactose metabolic pathways were significantly enriched., Conclusion: Our study identified two population-specific novel loci for AL, expanding our understanding of the genetic basis of AL and providing evidence for a role of the nervous system and glucose metabolism in myopia pathogenesis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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193. Differences in choroidal responses to near work between myopic children and young adults.
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Liu M, Wang Y, Li H, Zhao Y, Ma M, Xu S, Wei X, Xu R, Tian R, Zhou X, and Wu H
- Abstract
Background: Near work is generally considered as a risk factor for myopia onset and progression. This study aimed to investigate the choroidal responses to a brief-period of near work in children and young adults., Methods: Thirty myopic medical students (aged 18-28 years) and 30 myopic children (aged 8-12 years) participated in this study. The submacular total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI) and choriocapillaris flow deficit (CcFD), as well as subfoveal choroidal thickness (SFCT) were measured with swept-source optical coherence tomography/optical coherence tomography angiography (SS-OCT/OCTA) before and immediately after 20 min, 40 min, 60 min of near work at a distance of 33 cm., Results: In adults, 20 min of near work induced a significant reduction in SFCT (- 5.1 ± 6.5 μm), LA [(- 19.2 ± 18.6) × 10
3 μm2 ], SA [(- 8.2 ± 12.6) × 103 μm2 ] and TCA [(- 27.4 ± 24.9) × 103 μm2 ] (all P < 0.01). After 40 min of near work, LA was still reduced [(- 9.4 ± 18.3) × 103 μm2 ], accompanied with a decreased CVI (- 0.39% ± 0.70%) and an increased CcFD (0.30% ± 0.78%) (all P < 0.05). After 60 min of near work, CVI was still reduced (- 0.28% ± 0.59%), and CcFD was still increased (0.37% ± 0.75%) (all P < 0.05). In children, 20 min of near work induced a significant increase in CcFD (0.55% ± 0.64%), while 60 min of near work induced increases in SA [(7.2 ± 13.0) × 103 μm2 ] and TCA [(9.7 ± 25.3) × 103 μm2 ] and a reduction in CVI (- 0.28% ± 0.72%) (all P < 0.05). Children exhibited lower near work-induced LA and TCA reduction than adults, with a mean difference of - 0.86% and - 0.82%, respectively (all P < 0.05)., Conclusions: The temporal characteristics and magnitude of changes of choroidal vascularity and choriocapillaris perfusion during near work was not identical between children and adults. The initial response to near work was observed in choriocapillaris in children, whereas it was observed in the medium- and large-sized vessels in adults., Trial Registration: Clinical Trial Registry (ChiCTR), ChiCTR2000040205. Registered on 25 November 2020, https://www.chictr.org.cn/bin/project/edit?pid=64501 ., (© 2024. The Author(s).)- Published
- 2024
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194. Augmentation of scleral glycolysis promotes myopia through histone lactylation.
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Lin X, Lei Y, Pan M, Hu C, Xie B, Wu W, Su J, Li Y, Tan Y, Wei X, Xue Z, Xu R, Di M, Deng H, Liu S, Yang X, Qu J, Chen W, Zhou X, and Zhao F
- Subjects
- Animals, Guinea Pigs, Mice, Sclera metabolism, Lactic Acid metabolism, Glycolysis, Hypoxia metabolism, Histones metabolism, Myopia genetics, Myopia metabolism
- Abstract
Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
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195. The Role of Retinal Dopamine D1 Receptors in Ocular Growth and Myopia Development in Mice.
- Author
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Shu Z, Chen K, Wang Q, Wu H, Zhu Y, Tian R, Yan W, Huang Q, Zhang C, Xiong W, Qu J, Zhou X, and Huang F
- Subjects
- Male, Mice, Animals, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine pharmacology, Mice, Inbred C57BL, Retina metabolism, Receptors, Dopamine D1 metabolism, Dopamine metabolism, Myopia genetics, Myopia metabolism
- Abstract
Dopamine is a key neurotransmitter in the signaling cascade controlling ocular refractive development, but the exact role and site of action of dopamine D1 receptors (D1Rs) involved in myopia remains unclear. Here, we determine whether retinal D1Rs exclusively mediate the effects of endogenous dopamine and systemically delivered D1R agonist or antagonist in the mouse form deprivation myopia (FDM) model. Male C57BL/6 mice subjected to unilateral FDM or unobstructed vision were divided into the following four groups: one noninjected and three groups that received intraperitoneal injections of a vehicle, D1R agonist SKF38393 (18 and 59 nmol/g), or D1R antagonist SCH39166 (0.1 and 1 nmol/g). The effects of these drugs on FDM were further assessed in Drd1 -knock-out ( Drd1 -KO), retina-specific conditional Drd1 -KO ( Drd1 -CKO) mice, and corresponding wild-type littermates. In the visually unobstructed group, neither SKF38393 nor SCH39166 affected normal refractive development, whereas myopia development was attenuated by SKF38393 and enhanced by SCH39166 injections. In Drd1 -KO or Drd1 -CKO mice, however, these drugs had no effect on FDM development, suggesting that activation of retinal D1Rs is pertinent to myopia suppression by the D1R agonist. Interestingly, the development of myopia was unchanged by either Drd1 -KO or Drd1 -CKO, and neither SKF38393 nor SCH39166 injections, nor Drd1 -KO, affected the retinal or vitreal dopamine and the dopamine metabolite DOPAC levels. Effects on axial length were less marked than effects on refraction. Therefore, activation of D1Rs, specifically retinal D1Rs, inhibits myopia development in mice. These results also suggest that multiple dopamine D1R mechanisms play roles in emmetropization and myopia development. SIGNIFICANCE STATEMENT While dopamine is recognized as a "stop" signal that inhibits myopia development (myopization), the location of the dopamine D1 receptors (D1Rs) that mediate this action remains to be addressed. Answers to this key question are critical for understanding how dopaminergic systems regulate ocular growth and refraction. We report here the results of our study showing that D1Rs are essential for controlling ocular growth and myopia development in mice, and for identifying the retina as the site of action for dopaminergic control via D1Rs. These findings highlight the importance of intrinsic retinal dopaminergic mechanisms for the regulation of ocular growth and suggest specific avenues for exploring the retinal mechanisms involved in the dopaminergic control of emmetropization and myopization., (Copyright © 2023 the authors.)
- Published
- 2023
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196. Spontaneously Myopic Guinea Pig: Model of Early Pathologic Myopia.
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Zhang Y, Tang W, Liang J, Zhou X, Chen S, and Zhi Z
- Subjects
- Guinea Pigs, Animals, Anterior Eye Segment, Refraction, Ocular, Sclera, Myopia, Posterior Eye Segment, Hyperopia
- Abstract
Purpose: To evaluate whether pigmented guinea pigs with spontaneous myopia present characteristic changes of pathologic myopia., Methods: The fundus images of guinea pigs (3 weeks old) were graded according to fundus tessellation (FT) degree. Biometric parameters, including refraction, vitreous chamber depth (VCD), and axial length (AL), were measured at ages 21 and 43 days. Some of these animals were divided into three groups: hyperopic without FT (H w/o FT), myopic without FT (M w/o FT), and myopic with FT (M w/ FT). The horizontal and vertical radii of curvature of posterior sclera (RP-H and RP-V, respectively) and the radii of curvature and arc lengths of superior sclera (RS and LS, respectively), inferior sclera (RI and LI, respectively), nasal sclera (RN and LN, respectively), and temporal sclera (RT and LT) were evaluated by Fuji., Results: The fundi were graded as type A or type B (both without FT), type C (mild FT), or type D (severe FT). The prevalence of FT was correlated with myopic refraction, longer VCD, and longer AL. Eyes of M w/FT animals had shorter RP-H and RP-V, longer RS and RT, and longer LS and LT than eyes of H w/o FT or M w/o FT animals. Refractions shifted toward hyperopia in eyes lacking FT, but not in eyes having FT. The changes in VCD were consistent with the changes in refraction. This relatively myopic shift in refraction and shortening of VCD were found only in myopic eyes with FT, but not in myopic eyes without FT., Conclusions: Spontaneously myopic guinea pig eyes have a high prevalence of FT. Myopic eyes with FT presented characteristic signs of pathologic myopia.
- Published
- 2023
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197. Choroidal vasculature act as predictive biomarkers of long-term ocular elongation in myopic children treated with orthokeratology: a prospective cohort study.
- Author
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Wu H, Peng T, Zhou W, Huang Z, Li H, Wang T, Zhang J, Zhang K, Li H, Zhao Y, Qu J, Lu F, Zhou X, and Jiang J
- Abstract
Background: Despite receiving orthokeratology (ortho-k), the efficacy of retarding ocular elongation during myopia varies among myopic children. The current study aimed to investigate the early changes of choroidal vasculature at one month after ortho-k treatment and its association with one-year ocular elongation, as well as the role of such choroidal responses in predicting the one-year control efficacy of ortho-k treatment., Methods: A prospective cohort study was conducted in myopic children treated with ortho-k. Myopic children aged between 8 and 12 years who were willing to wear ortho-k lenses were recruited consecutively from the Eye Hospital of Wenzhou Medical University. Subfoveal choroidal thickness (SFCT), submacular total choroidal luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow deficit (CcFD) were evaluated by optical coherence tomography (OCT) and OCT angiography over a one-year period., Results: Fifty eyes from 50 participants (24 males) who finished one-year follow-ups as scheduled were included, with a mean age of 10.31 ± 1.45 years. The one-year ocular elongation was 0.19 ± 0.17 mm. The LA (0.03 ± 0.07 mm
2 ), SA (0.02 ± 0.05 mm2 ) increased proportionally after one-month of ortho-k wear (both P < 0.01), as did the SFCT (10.62 ± 19.98 μm, P < 0.001). Multivariable linear regression analyses showed that baseline CVI (β = - 0.023 mm/1%, 95% CI: - 0.036 to - 0.010), one-month LA change (β = - 0.009 mm/0.01 mm2 , 95% CI: - 0.014 to - 0.003), one-month SFCT change (β = - 0.035 mm/10 µm, 95% CI: - 0.053 to - 0.017) were independently associated with one-year ocular elongation during ortho-k treatment after adjusting with age and sex (all P < 0.01). The area under the receiver operating characteristic curve of prediction model including baseline CVI, one-month SFCT change, age, and sex achieved 0.872 (95% CI: 0.771 to 0.973) for discriminating children with slow or fast ocular elongation., Conclusions: Choroidal vasculature is associated with ocular elongation during ortho-k treatment. Ortho-k treatment induces increases in choroidal vascularity and choroidal thickness as early as one month. Such early changes can act as predictive biomarkers of myopia control efficacy over a long term. The utilization of these biomarkers may help clinicians identify children who can benefit from ortho-k treatment, and thus has critical implications for the management strategies towards myopia control., (© 2023. The Author(s).)- Published
- 2023
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198. Choroidal Circulation in 8- to 30-Year-Old Chinese, Measured by SS-OCT/OCTA: Relations to Age, Axial Length, and Choroidal Thickness.
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Wang Y, Liu M, Xie Z, Wang P, Li X, Yao X, Tian J, Han Y, Chen X, Xu Z, Mao X, Zhou X, Qu J, and Wu H
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- Humans, Child, Adolescent, Young Adult, Adult, Cross-Sectional Studies, East Asian People, Choroid blood supply, Tomography, Optical Coherence methods, Myopia pathology
- Abstract
Purpose: The purpose of this study was to evaluate and explore the determinants of choroidal vascularity and choriocapillaris perfusion in a Chinese population aged 8 to 30 years old., Methods: Three hundred eighty eyes from 380 subjects aged 8 to 30 years were included in this cross-sectional study. Submacular choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), and choriocapillaris flow deficit (CcFD) were estimated using images obtained from optical coherence tomography (OCT)., Results: In this population, the mean ChT was 260.4 ± 63.3 µm, TCA was 1.56 ± 0.38 mm2, LA was 0.94 ± 0.25 mm2, and SA was 0.62 ± 0.15 mm2. The mean CVI was 60.25 ± 3.21% and CcFD was 11.95 ± 1.98%. Multivariable analyses showed that higher CVI and LA was associated with older age, thicker ChT, and shorter AL; and lower CcFD was associated with shorter AL. However, the associations were not uniformly rectilinear between CcFD and age. Specifically, CcFD was positively associated with age in subjects ≤19 years old and negatively associated with age in subjects >19 years old., Conclusions: Development of the choroidal medium- and large-sized vascular layers and choriocapillaris was different across patients aged 8 to 30 years old. Greater axial length was associated with attenuated choroidal circulation. Choroidal thickness correlated well with choroidal vascularity, but not with choriocapillaris perfusion. Further comprehensive and longitudinal assessment of choroidal vasculature and choriocapillaris perfusion will help greatly to understand the physiological and pathological mechanisms responsible for myopia.
- Published
- 2023
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199. IMI-The Dynamic Choroid: New Insights, Challenges, and Potential Significance for Human Myopia.
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Ostrin LA, Harb E, Nickla DL, Read SA, Alonso-Caneiro D, Schroedl F, Kaser-Eichberger A, Zhou X, and Wildsoet CF
- Subjects
- Animals, Humans, Choroid physiology, Bruch Membrane, Models, Animal, Tomography, Optical Coherence methods, Axial Length, Eye, Myopia
- Abstract
The choroid is the richly vascular layer of the eye located between the sclera and Bruch's membrane. Early studies in animals, as well as more recent studies in humans, have demonstrated that the choroid is a dynamic, multifunctional structure, with its thickness directly and indirectly subject to modulation by a variety of physiologic and visual stimuli. In this review, the anatomy and function of the choroid are summarized and links between the choroid, eye growth regulation, and myopia, as demonstrated in animal models, discussed. Methods for quantifying choroidal thickness in the human eye and associated challenges are described, the literature examining choroidal changes in response to various visual stimuli and refractive error-related differences are summarized, and the potential implications of the latter for myopia are considered. This review also allowed for the reexamination of the hypothesis that short-term changes in choroidal thickness induced by pharmacologic, optical, or environmental stimuli are predictive of future long-term changes in axial elongation, and the speculation that short-term choroidal thickening can be used as a biomarker of treatment efficacy for myopia control therapies, with the general conclusion that current evidence is not sufficient.
- Published
- 2023
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200. Calcipotriol Attenuates Form Deprivation Myopia Through a Signaling Pathway Parallel to TGF-β2-Induced Increases in Collagen Expression.
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Jiao S, Reinach PS, Huang C, Yu L, Zhuang H, Ran H, Zhao F, Srinivasalu N, Qu J, and Zhou X
- Subjects
- Humans, Animals, Mice, Mice, Inbred C57BL, Collagen metabolism, Calcitriol pharmacology, Calcitriol metabolism, Signal Transduction, Sclera metabolism, Transforming Growth Factor beta2 pharmacology, Transforming Growth Factor beta2 metabolism, Myopia genetics
- Abstract
Purpose: To determine the role of calcipotriol, a vitamin D3 analogue, in myopia development and altering the expression of scleral α1 chain of type I collagen (Col1α1) in mice. We also aimed to identify if the signaling pathway mediating the above changes is different from the one involved in transforming growth factor β2 (TGF-β2)-mediated increases of COL1A1 in cultured human scleral fibroblasts (HSFs)., Methods: C57BL/6J mice were either intraperitoneally injected with calcipotriol and subjected to form deprivation (FD) or exposed to normal refractive development for 4 weeks. Scleral vitamin D receptor (Vdr) expression was knocked down using a Sub-Tenon's capsule injection of an adeno-associated virus-packaged short hairpin RNA (AAV8-shRNA). Refraction and biometric measurements evaluated myopia development. A combination of knockdown and induction strategies determined the relative contributions of the vitamin D3 and the TGF-β2 signaling pathways in modulating COL1A1 expression in HSFs., Results: Calcipotriol injections suppressed FD-induced myopia (FDM), but it had no significant effect on normal refractive development. AAV8-shRNA injection reduced Vdr mRNA expression by 42% and shifted the refraction toward myopia (-3.15 ± 0.99D, means ± SEM) in normal eyes. In HSFs, VDR knockdown reduced calcipotriol-induced rises in COL1A1 expression, but it did not alter TGF-β2-induced increases in COL1A1 expression. Additionally, TGF-β2 augmented calcipotriol-induced rises in COL1A1 expression. TGF-β receptor (TGFBRI/II) knockdown blunted TGF-β2-induced increases in COL1A1 expression, whereas calcipotriol-induced increases in VDR and COL1A1 expression levels were unaltered., Conclusions: Scleral vitamin D3 inhibits myopia development in mice, potentially by activating a VDR-dependent signaling pathway and increasing scleral COL1A1 expression levels.
- Published
- 2023
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