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Abstract Purpose Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. Methods Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. Results Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. Conclusion This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.

In recent years, concerns have escalated regarding eye health problems arising from Light-emitting diode (LED), which emits high-energy blue light (BL), potentially causing corneal epithelial dysfunctions (CEpD). Nevertheless, the mechanisms underlying this damage remain poorly comprehended. This study endeavors to explore the specific mechanisms through which BL exposure induces CEpD. The study carried out diverse assays and treatments to investigate the toxicological effects of BL exposure. 48 hours (h) of 440 nm of BL exposure decreased the migration of human corneal epithelial cells (hCEpCs) while augmenting reactive oxygen species (ROS) production and apoptosis. RNA-Sequencing and bioinformatic analysis indicated that cellular oxidation and reduction equilibrium, wound healing, the positive regulation of the apoptotic process, and the Phosphoinositide 3-kinase (PI3K)/AKT pathway were significantly influenced by BL exposure. Treatment with N-acetylcysteine (NAC), a ROS scavenger, restored cell viability and AKT/S6 kinase (S6K) activation, suggesting the involvement of ROS in BL-induced damage. NAC also reversed BL-induced apoptosis and migration. Blocking AKT/S6K replicated detrimental effects, while pre-treatment with SC79 (SC), an AKT activator, alleviated the changes caused by BL exposure in hCEpCs. Furthermore, in mice, the combination of AKT inhibition and BL exposure led to CEpD. However, treatment with SC and NAC restored CEpD caused by BL exposure. These results imply that the regulation of the ROS/PI3K/AKT/S6K axis is implicated in BL-induced CEpD. Collectively, this study offers insights into the molecular mechanisms of BL-induced CEpD and proposes targeting the ROS/PI3K/AKT/S6K cascade as a potential therapeutic approach. The findings contribute to ocular health knowledge and establish the basis for developing interventions to safeguard the cornea from the detrimental effects of excessive BL exposure.

Abstract Objective To construct a nutrition support program for middle-aged and elderly patients with acute decompensated heart failure (ADHF) during hospitalization. Methods Based on the JBI Evidence-Based Health Care Model as the theoretical framework, the best evidence was extracted through literature analysis and a preliminary nutrition support plan for middle-aged and elderly ADHF patients during hospitalization was formed. Two rounds of expert opinion consultation were conducted using the Delphi method. The indicators were modified, supplemented and reduced according to the expert’s scoring and feedback, and the expert scoring was calculated. Results The response rates of the experts in the two rounds of consultation were 86.7% and 100%, respectively, and the coefficient of variation (CV) for each round was between 0.00% and 29.67% (all

Abstract Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.

Abstract In the early stages of diabetic retinopathy (DR), diabetes-related hyperglycemia directly inhibits the AKT signaling pathway by increasing oxidative stress or inhibiting growth factor expression, which leads to retinal cell apoptosis, nerve proliferation and fundus microvascular disease. However, due to compensatory vascular hyperplasia in the late stage of DR, the vascular endothelial growth factor (VEGF)/phosphatidylinositol 3 kinase (PI3K)/AKT cascade is activated, resulting in opposite levels of AKT regulation compared with the early stage. Studies have shown that many factors, including insulin, insulin-like growth factor-1 (IGF-1), VEGF and others, can regulate the AKT pathway. Disruption of the insulin pathway decreases AKT activation. IGF-1 downregulation decreases the activation of AKT in DR, which abrogates the neuroprotective effect, upregulates VEGF expression and thus induces neovascularization. Although inhibiting VEGF is the main treatment for neovascularization in DR, excessive inhibition may lead to apoptosis in inner retinal neurons. AKT pathway substrates, including mammalian target of rapamycin (mTOR), forkhead box O (FOXO), glycogen synthase kinase-3 (GSK-3)/nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-B (NF-κB), are a research focus. mTOR inhibitors can delay or prevent retinal microangiopathy, whereas low mTOR activity can decrease retinal protein synthesis. Inactivated AKT fails to inhibit FOXO and thus causes apoptosis. The GSK-3/Nrf2 cascade regulates oxidation and inflammation in DR. NF-κB is activated in diabetic retinas and is involved in inflammation and apoptosis. Many pathways or vital activities, such as the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathways, interact with the AKT pathway to influence DR development. Numerous regulatory methods can simultaneously impact the AKT pathway and other pathways, and it is essential to consider both the connections and interactions between these pathways. In this review, we summarize changes in the AKT signaling pathway in DR and targeted drugs based on these potential sites.

Abstract Background To explore differential metabolites in the aqueous humor of patients with different axial lengths and their correlations with axial length and choroidal parameters. Methods In this study, we included 12 patients with axial lengths less than 24 mm, 11 patients with axial lengths between 24 and 26 mm, and 11 patients with axial lengths greater than 26 mm. We collected their aqueous humor samples during cataract surgery for liquid chromatography-mass spectrometry metabolomic analysis. Simultaneously, we collected relevant clinical parameters such as axial length, subfoveal choroidal thickness, and choroidal vascular index. Correlations between clinical data, differential metabolites, and clinical indicators were analyzed. In addition, we plotted receiver operating characteristic curves. Results The results showed that axial length was significantly negatively correlated with choroidal thickness (r=-0.7446, P

Summary: This study aimed to investigate the effects of long-term pollution from different wavelengths of light on the corneal epithelium (CE) and identify potential biomarkers. Rabbits were exposed to red, green, blue, white, and environmental light for 6 weeks. The CE was assessed using various techniques such as fluorescein sodium staining, transcriptome sequencing, electron microscopy, and molecular assays. In human corneal epithelial cells (hCECs), the downregulation of vascular cell adhesion molecule 1 (VCAM1) in response to blue light (BL) pollution was observed. This downregulation of VCAM1 inhibited migration, increased reactive oxygen species (ROS) levels, and apoptosis, and inhibited the AKT/p70 S6 kinase cascade in hCECs. Animal experiments confirmed that BL pollution caused similar effects on the rabbit cornea, including increased ROS production, apoptosis, delayed wound healing, and decreased VCAM1 expression. Overall, BL-induced VCAM1 downregulation may impair CE and wound healing and promote ROS and apoptosis in vitro and in vivo.

Nearly all modern life depends on artificial light; however, it does cause health problems. With certain restrictions of artificial light emitting technology, the influence of the light spectrum is inevitable. The most remarkable problem is its overload in the short wavelength component. Short wavelength artificial light has a wide range of influences from ocular development to mental problems. The visual neuronal pathway, as the primary light-sensing structure, may contain the fundamental mechanism of all light-induced abnormalities. However, how the artificial light spectrum shapes the visual neuronal pathway during development in mammals is poorly understood. We placed C57BL/6 mice in three different spectrum environments (full-spectrum white light: 400–750 nm; violet light: 400 ± 20 nm; green light: 510 ± 20 nm) beginning at eye opening, with a fixed light time of 7:00–19:00. During development, we assessed the ocular axial dimension, visual function and retinal neurons. After two weeks under short wavelength conditions, the ocular axial length (AL), anterior chamber depth (ACD) and length of lens thickness, real vitreous chamber depth and retinal thickness (LLVR) were shorter, visual acuity (VA) decreased, and retinal electrical activity was impaired. The density of S-cones in the dorsal and ventral retinas both decreased after one week under short wavelength conditions. In the ventral retina, it increased after three weeks. Retinal ganglion cell (RGC) density and axon thickness were not influenced; however, the axonal terminals in the lateral geniculate nucleus (LGN) were less clustered and sparse. Amacrine cells (ACs) were significantly more activated. Green light has few effects. The KEGG and GO enrichment analyses showed that many genes related to neural circuitry, synaptic formation and neurotransmitter function were differentially expressed in the short wavelength light group. In conclusion, exposure to short wavelength artificial light in the early stage of vision-dependent development in mice delayed the development of the visual pathway. The axon terminus structure and neurotransmitter function may be the major suffering.

Abstract Background Pathogenesis of posterior capsular opacification (PCO) was related to pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). It has been reported that blue light could have an effect on EMT. This study aims to elucidate the role and potential mechanism of autophagy in EMT after blue light exposure in LECs. Methods HLE-B3 cells were treated with TGF-β2 with different concentration and time to induce EMT as a model of PCO in vitro. Cells were exposed to blue light with or without TGF-β2. The expression levels of EMT-associated markers were analyzed by qRT-PCR, western blotting and cell migration ability was determined by transwell migration assay and wound healing assay. The expressions of autophagy-related proteins were analyzed by western blotting, immunofluorescence and transmission electron microscopy. Rapamycin and chloroquine were utilized in cells for autophagy activation and inhibition. Results TGF-β2 induced autophagy activation during EMT progression in HLE-B3 cells in a dose- and time-dependent manner. Blue light exposure inhibited TGF-β2-induced EMT characterized by inhibited expression of EMT related markers and reduced migration capacity. Meanwhile, blue light exposure impaired autophagy activated by TGF-β2. Furthermore, Autophagy activation with rapamycin rescued EMT attenuated by blue light. Autophagy inhibition with chloroquine reduced TGF-β2-induced EMT in HLE-B3 cells. Conclusion Blue light exposure had inhibited effects on TGF-β2-induced EMT in LECs through autophagy impairment, which provides a new insight on prevention and treatment of PCO.

Abstract Background Changes in the retina and choroid blood vessels are regularly observed in myopia. However, if the retinal glial cells, which directly contact blood vessels, play a role in mammalian myopia is unknown. We aimed to explore the potential role and mechanism of retinal glial cells in form deprived myopia. Methods We adapted the mice form-deprivation myopia model by covering the right eye and left the left eye open for control, measured the ocular structure with anterior segment optical coherence tomography, evaluated changes in the morphology and distribution of retinal glial cells by fluorescence staining and western blotting; we also searched the online GEO databases to obtain relative gene lists and confirmed them in the form-deprivation myopia mouse retina at mRNA and protein level. Results Compared with the open eye, the ocular axial length (3.54 ± 0.006 mm v.s. 3.48 ± 0.004 mm, p = 0.027) and vitreous chamber depth (3.07 ± 0.005 mm v.s. 2.98 ± 0.006 mm, p = 0.007) in the covered eye became longer. Both glial fibrillary acidic protein and excitatory amino acid transporters 4 elevated. There were 12 common pathways in human myopia and anoxic astrocytes. The key proteins were also highly relevant to atropine target proteins. In mice, two common pathways were found in myopia and anoxic Müller cells. Seven main genes and four key proteins were significantly changed in the mice form-deprivation myopia retinas. Conclusion Retinal astrocytes and Müller cells were activated in myopia. They may response to stimuli and secretory acting factors, and might be a valid target for atropine.

Abstract Phosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.

Abstract Background Myopia is hypothesized to be influenced by environmental light conditions. For example, it has been shown that colour and temporal frequency of flickering light affect emmetropisation in animals. Considering the omnipresence of flickering light in our daily life, we decided to analyze the effect of colour flickers on variability of the accommodation response (VAR) in emmetropes and myopes. Methods We measured the dynamic accommodative responses of 19 emmetropic and 22 myopic adults using a Grand Seiko WAM-5500 open-field autorefractor. The subjects focused for more than 20 s on a black Snellen E target against three different backgrounds made up of three colour flicker combinations (red/green, red/blue and blue/green) and under five frequency conditions (0.20 Hz, 0.50 Hz, 1.00 Hz, 1.67 Hz, and 5.00 Hz). Results Flicker frequency and colour both had a significant effect on VAR. Lower frequencies were associated with larger variability. Colour had an effect only at low frequencies, and red/blue colour flicker resulted in the largest variability. The variability in myopes were larger than those in emmetropes. Conclusions These findings support the hypothesis that further studies on the colour and temporal frequency of flickering light can lead to a better understanding of the development and progression of myopia.

The pathogenesis of myopia is driven by genetic and environmental risk factors. Accommodation not only alters the curvature and shape of the lens but also involves contraction of the ciliary and extraocular muscles, which influences intraocular pressure (IOP). Scleral matrix remodeling has been shown to contribute to the biomechanical susceptibility of the sclera to accommodation-induced IOP fluctuations, resulting in reduced scleral thickness, axial length (AL) elongation, and axial myopia. The rise in IOP can increase the burden of scleral stretching and cause axial lengthening. Although the accommodation and IOP hypotheses were proposed long ago, they have not been validated. This review provides a brief and updated overview on studies investigating the potential role of accommodation and IOP in myopia progression.

Purpose: Glaucoma is characterized by optic nerve damage and retinal ganglion cell loss. The glycoprotein neuromedin B-associated (Gpnmb) gene is well-known to be involved in the glaucoma disease process. The purpose of this study is to identify a downstream gene through which Gpnmb affects the glaucoma phenotypes using a systems genetics approach. Methods: Retinal gene expression data for the BXD recombinant inbred (RI) strains (n=75) have previously been generated in our laboratory for a glaucoma study, and these data were used for genetic and bioinformatics analysis. Expression quantitative trait locus (eQTL) mapping and genetic correlation methods were used to identify a gene downstream of Gpnmb. Gene-set enrichment analysis was used to evaluate gene function and to construct coexpression networks. Results: The level of Gpnmb expression is associated with a highly statistically significant cis-eQTL. Stanniocalcin 1 (Stc1) has a significant trans-eQTL mapping to the Gpnmb locus. The expression of Gpnmb and Stc1 is highly correlated in the retina and other tissues, as well as with glaucoma-related phenotypes. Gene Ontology and pathway analysis showed that Stc1 and its covariates are highly associated with apoptosis, oxidative stress, and mitochondrial activity. A generated gene network indicated that Gpnmb and Stc1 are directly connected to and interact with other genes with similar biologic functions. Conclusions: These results suggest that Stc1 may be a downstream candidate of Gpnmb, and that both genes interact with other genes in a network to develop glaucoma pathogenesis through mechanisms such as apoptosis and oxidative stress.

Purpose To evaluate longitudinal changes in Implantable Collamer Lens phakic intraocular lens (pIOL) position after implantation. Setting Department of Ophthalmology, Zhejiang University, Hangzhou, China. Design Retrospective case series. Methods Myopic eyes that had pIOL implantation with a follow-up of at least 24 months were evaluated. Ultrasound biomicroscopy examinations were performed at each visit. Results The study enrolled 62 eyes (31 patients; 22 women, 9 men) ranging in age from 21 to 46 years. The manifest spherical equivalent ranged from -8.25 to -18.75 diopters. A significant increase (mean 36 μm ± 50 [SD]) in the endothelium-anterior pIOL distance occurred between 1 month and 3 months (P=.000); afterward, the distance decreased slowly (P>.05). The largest decrease (mean 47 ± 17 μm) in central vault occurred between 1 month and 3 months (P=.009). The largest decrease (mean 21 ± 14 μm) in peripheral vault occurred between 1 month and 3 months (P=.000). Conclusions A significant increase in the endothelium-anterior pIOL distance occurred from 1 month to 3 months postoperatively, after which a slight decrease occurred over time. Central vault and peripheral vault had a tendency to decrease over time. [ABSTRACT FROM AUTHOR]

Purpose: To describe the utility of using ultra-widefield digital fundus photography and ultra-widefield fluorescein angiography (UWFA) in the pediatric patient population to evaluate peripheral retinal pathology and to manage Coats' disease and familial exudative vitreoretinopathy (FEVR). Methods: Retrospective review of pediatric retinal patients with FEVR or Coats' disease who underwent ultra-widefield fundus photography and UWFA. Results: Eight patients were included in this case series. Five patients had the clinical diagnosis of FEVR, and two eyes of two patients with FEVR received UWFA-guided laser photocoagulation. Three patients were diagnosed as having Coats' disease and received UWFA-guided laser photocoagulation. Conclusions: Ultra-widefield fundus photography and UWFA can be used successfully as an outpatient procedure in the pediatric patient population without the necessity of examination under anesthesia and can aid the physician in the documentation and evaluation of peripheral retinal pathology. UWFA can also assist in directing laser photocoagulation in the treatment of pediatric retinal diseases. [ABSTRACT FROM AUTHOR]