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Introduction: Complex corneal conditions present surgical challenges and necessitate innovation. Here, we present two cases where we performed intraocular lens trans-scleral fixation using the double-needle Yamane technique, followed by penetrating keratoplasty and vitrectomy using a temporary Landers wide-field keratoprosthesis., Case Presentation: Case 1 involved a 70-year-old man with an aphakic eye of bullous keratopathy and corneal opacity owing to multiple penetrating and endothelial keratoplasty, endophthalmitis, and herpetic keratitis. His visual acuity was counting fingers at 20 cm before surgery. Penetrating keratoplasty with vitrectomy and intraocular lens scleral fixation was performed using the double-needle Yamane technique, and 10 months postoperatively, his best-corrected visual acuity improved to 0.6, presenting a clear cornea. Case 2 involved a 62-year-old man who underwent penetrating keratoplasty twice for corneal perforation and therapeutic penetrating keratoplasty with vitrectomy for traumatic globe rupture, resulting in the loss of the intraocular lens. The patient exhibited graft failure, and his best-corrected visual acuity was 0.03. Utilizing a temporary Landers wide-field keratoprosthesis, we performed penetrating keratoplasty and intraocular lens trans-scleral fixation without complications. His final best-corrected visual acuity improved to 0.15 with a clear cornea., Conclusions: Trans-scleral fixation of intraocular lens with penetrating keratoplasty, using temporary Landers wide-field keratoprosthesis, yielded positive clinical outcomes without serious complications., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Corneal graft detachment is a major postoperative complication of Descemet's stripping automated endothelial keratoplasty (DSAEK). When a corneal graft becomes detached, corneal endothelial function generally fails, and repeat corneal transplantation is required. Herein, we report a rare case in which a transparent cornea was maintained after the removal of a dislocated DSAEK graft., Case Presentation: A 79-year-old woman with a residual lens cortex who had undergone cataract surgery was referred to our hospital. The cortex was removed, and bullous keratopathy progressed. Six months after the initial surgery, DSAEK was performed under topical anesthesia without any complications. Although the corneal graft had attached fairly well, it detached from the host cornea 3 weeks later. Two months after DSAEK, an air tamponade was used to treat the anterior chamber with single interrupted suturing; however, the graft detached again, except for the suture site. Because the detached cornea became cloudy in the anterior chamber, it was surgically removed 8 months after DSAEK. Accordingly, the host cornea transparency improved to a best-corrected visual acuity of 0.8 with a rigid gas permeable lens and a central corneal thickness of 580 μm. The corneal endothelial cell density was 995 cells/mm 2 ., Conclusion: Removal of the corneal graft from the dislocated cloudy graft improved the visual acuity of this patient after DSAEK. The condition of the cornea should be carefully monitored after corneal endothelial transplantation, even after the graft has been dislocated., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Inflammatory juvenile conjunctival nevus (IJCN) is a rare condition affecting both children and adolescents. It has misleading clinical and histopathological features; therefore, careful assessment is necessary. We present a case of IJCN with a rare pathological type and misleading histopathological features., Case Presentation: A 13-year-old girl with IJCN in the right eye was treated with antiallergic and steroid eye drops but showed no response and was referred to our hospital for excisional biopsy. Slit-lamp examination revealed a nonpigmented juxtalimbal tumor in the right eye. Histopathologically, nevus cells with mild nuclear atypia proliferated within the conjunctival epithelium. Confluent growth of junctional nests, conjunctival cysts, and prominent inflammatory infiltration were also observed. Considering the young age of the patient and immunohistochemical characteristics (HMB-45, SOX10, p16 and Ki-67), the patient was finally diagnosed with IJCN. IJCN has three pathological subtypes - compound, subepithelial, and junctional - depending on the location of the nevus cells. This case was diagnosed as a rare junctional type, as most of the examined sections only showed lesions within the epithelium; no lesions were clearly identified extending beneath the epithelium., Conclusion: The pathological diagnosis of IJCN is difficult because some features of IJCN suggest malignancy. Detailed microscopic examination, immunohistochemical staining, and the patient's young age helped render a final diagnosis., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: Corneal scars after infectious keratitis lead to insufficient transparency and irregular astigmatism, affecting visual acuity; therefore, they should be accurately evaluated to estimate visual function. This study aimed to quantitatively evaluate corneal irregularity and scarring after infectious keratitis using anterior segment optical coherence tomography (AS-OCT)., Methods: This was an observational clinical study. We included patients who had corneal scarring after treatment of infectious keratitis between 2014 and 2021 at University of Tokyo Hospital. We retrospectively examined best spectacle-corrected visual acuity (BSCVA), average keratometric power, central corneal thickness (CCT), and four components of the Fourier harmonic analysis including spherical and asymmetry components, as well as regular astigmatism and higher-order irregularity. We included anterior and posterior corneal data and compared results with those of contralateral healthy eyes. Additionally, we quantitatively evaluated the densitometry of the cornea obtained using AS-OCT., Results: A total of 122 eyes of 61 patients were examined; male predominance was observed (n = 37), and the mean patient age was 55.3 ± 19.4 years. Comparisons with contralateral healthy eyes showed that BSCVA worsened (0.30 ± 0.83 and 0.93 ± 1.36 logMAR, respectively, P = 0.003), and CCT (531.1 ± 46.2 and 591.8 ± 132.4 μm, respectively, P < 0.001) and corneal densitometry (84.4 ± 11.8 and 111.9 ± 19.2 grayscale units, respectively, P < 0.001) increased significantly in affected eyes. The asymmetry component and higher-order irregularities that were not corrected with spectacles significantly increased (both P < 0.001), and there were no significant differences in the changes among the bacterial, fungal, herpetic, and acanthamoeba types of keratitis., Conclusion: Corneal scarring persisted after treatment for infectious keratitis, and the asymmetry and irregularities of corneal astigmatism increased as visual acuity deteriorated. AS-OCT with the Fourier harmonic analysis was useful for evaluating corneal topographic changes in patients with corneal scarring after keratitis., (© 2023. The Author(s).)

Mammalian taste bud cells are composed of several distinct cell types and differentiated from surrounding tongue epithelial cells. However, the detailed mechanisms underlying their differentiation have yet to be elucidated. In the present study, we examined an Ascl1-expressing cell lineage using circumvallate papillae (CVP) of newborn mice and taste organoids (three-dimensional self-organized tissue cultures), which allow studying the differentiation of taste bud cells in fine detail ex vivo. Using lineage-tracing analysis, we observed that Ascl1 lineage cells expressed type II and III taste cell markers both CVP of newborn mice and taste organoids. However, the coexpression rate in type II cells was lower than that in type III cells. Furthermore, we found that the generation of the cells which express type II and III cell markers was suppressed in taste organoids lacking Ascl1-expressing cells. These findings suggest that Ascl1-expressing precursor cells can differentiate into both type III and a subset of type II taste cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study was to investigate the sectorized corneal thickness of eyes with corneal endothelial dysfunction using anterior-segment optical coherence tomography., Methods: We retrospectively collected anterior-segment optical coherence tomography data conducted before endothelial keratoplasty on 53 eyes of 53 patients with corneal endothelial dysfunctions including Fuchs endothelial corneal dystrophy, bullous keratopathy (BK) after trabeculectomy, and BK after laser iridotomy and from 18 normal eyes of 18 subjects. The imaging points were divided into 17 sectors. The mean for each sector was calculated and compared with the corresponding superior/inferior and temporal/nasal sectors., Results: In the normal eyes, the superior sectors were thicker than the inferior and the temporal sectors thinner than the nasal. In the diseased eyes, the superior sectors were thicker than the inferior in all subgroups; however, this tendency was no longer observed after the values were divided by the mean for the normal eyes. No significant differences were found on horizontal comparisons; however, after the values were divided by the mean for the normal eyes, the temporal sectors were thicker than the nasal. When comparing the values between the with-hole and the without-hole sides in the BK after laser iridotomy eyes, the sectors on the with-hole side were thicker than the other side., Conclusions: Corneal thickness of endothelial dysfunction was thicker in the superior sectors than the inferior but at a similar level to normal eyes. No significant differences were found for horizontal comparisons but, based on comparison with the normal eyes, the temporal sectors were thicker than the nasal., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The right and left mandibular processes derived from the first branchial arch grow toward the midline and fuse to create the rostral tip region of the mandible during mandibular development. Severe and mild cases of failure in this process results in rare median cleft of the lower lip and cleft chin, respectively. The detailed molecular mechanisms of mandibular tip formation are unknown. We hypothesize that the Msx1 gene is involved in mandibular tip development, because Msx1 has a central role in other craniofacial morphogenesis processes, such as teeth and the secondary palate development. Normal Msx1 expression was observed in the rostral end of the developing mandible; however, a reduced expression of Msx1 was observed in the soft tissue of the mandibular tip than in the lower incisor bud region. The rostral tip of the right and left mandibular processes was unfused in both control and Msx1-null (Msx1 -/- ) mice at embryonic day (E) 12.5; however, a complete fusion of these processes was observed at E13.5 in the control. The fused processes exhibited a conical shape in the control, whereas the same region remained bifurcated in Msx1 -/- . This phenotype occurred with 100% penetrance and was not restored at subsequent stages of development. Furthermore, Meckel's cartilage in addition to the outline surface soft tissues was also unfused and bifurcated in Msx1 -/- from E14.5 onward. The expression of phosho-Smad1/5, which is a mediator of bone morphogenetic protein (Bmp) signaling, was downregulated in the mandibular tip of Msx1 -/- at E12.5 and E13.5, probably due to the downregulated Bmp4 expression in the neighboring lower incisor bud. Cell proliferation was significantly reduced in the midline region of the mandibular tip in Msx1 -/- at the same developmental stages in which downregulation of pSmad was observed. Our results indicate that Msx1 is indispensable for proper mandibular tip development., Competing Interests: Declaration of conflicting interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: We aimed to identify pathogenic variations in the UbiA prenyltransferase domain-containing protein 1 (UBIAD1) gene in a Japanese family with Schnyder corneal dystrophy (SCD)., Study Design: Clinical study METHODS: Three clinically diagnosed SCD patients from a single pedigree participated. Patients 1 and 2 were 69- and 65-year-old sisters, and patient 3 was the 42-year-old daughter of patient 1. Blood samples from the patients were obtained for genetic analysis. Mutation screening of the two UBIAD1 exons was performed using polymerase chain reaction (PCR)-based DNA sequencing., Results: All participants were found to be heterozygous for the pathogenic missense variation c.695 A > G (p.Asn232Ser) in exon 2 of UBIAD1., Conclusion: This is the first report on the pathogenic UBIAD1 variation c.695 A > G (p.Asn232Ser) in a Japanese population. SCD is a rare corneal dystrophy, and further research on additional cases will aid in the elucidation of disease mechanisms and development of therapeutic strategies., (© 2022. Japanese Ophthalmological Society.)

Bullous keratopathy (BK) is known to present with corneal edema and Descemet's folds, which can cause corneal astigmatism. However, no report quantitatively evaluated BK astigmatism by separating it into regular and irregular astigmatism. This study investigated the regular and irregular astigmatism of the anterior and posterior corneal surface with Fourier harmonic analysis and anterior segment optical coherence tomography. Preoperative data from 43 eyes of 41 BK patients who received corneal endothelial transplantation were compared with the data from 43 eyes of 43 subjects without corneal disease. Anterior and posterior cylinder power, central corneal thickness (CCT) and thinnest corneal thickness were significantly greater in BK. With Fourier harmonic analysis, BK eyes were found to have significantly larger anterior and posterior regular astigmatism, asymmetry component and higher-order irregularity. Asymmetry component and higher-order irregularity that accounted for the posterior irregular astigmatism increased as CCT increased in BK. Higher-order irregularity in the posterior cornea also positively correlated with worsening best corrected visual acuity. Subgroup analysis found significant correlations between CCT and posterior higher-order irregularity for intraocular surgery and laser iridotomy, but not Fuchs endothelial corneal dystrophy. This study has significance in that it revealed the characteristics of the corneal posterior irregular astigmatism of BK., (© 2022. The Author(s).)

Background/purpose: Human periodontal ligament consists of elastic system fibers, mainly fibrillin-1 (FBN1). Periostin (POSTN) maintains periodontal homeostasis. A previous study showed that the expression of Postn in periodontal ligament cells was decreased in mice underexpressing Fbn1 . However, the relationship between FBN1 and POSTN is not fully understood in the context of mechanical stress. FBN1 contributes to transforming growth factor β1 (TGF-β1) activation; TGF-β1 upregulates the expression of POSTN in human periodontal ligament cells. This study examined whether FBN1 contributed to the maintenance of periodontal homeostasis in cultured human periodontal ligament cells., Materials and Methods: Human periodontal ligament fibroblasts (HPDLFs) were exposed to mechanical force via centrifugation. The expression of POSTN was examined by quantitative reverse transcription polymerase chain reaction. The phosphorylation of Smad2 in the TGF-β/Smad signaling pathway was monitored by western blotting., Results: The expression levels of FBN1 and POSTN were not significantly decreased by centrifugation. However, the expression of POSTN after centrifugation significantly decreased upon knockdown of FBN1 . The phosphorylation of Smad2 after centrifugation was decreased, regardless of FBN1 knockdown. Supplementation with 0.1 ng/ml recombinant human TGF-β1 rescued POSTN expression after centrifugation in HPDLFs upon knockdown of FBN1 ., Conclusion: FBN1 regulates the expression of POSTN to maintain periodontal homeostasis via TGF-β/Smad signaling during centrifugation., Competing Interests: The authors declare that they have no conflicts of interest., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

The purpose of this study was to evaluate corneal irregular astigmatism of patients with granular and lattice corneal dystrophy (GCD and LCD). 70 GCD, 35 LCD, and 81 control eyes were included. Anterior and posterior corneal topographic data obtained from anterior segment optical coherence tomography were expanded into four components via Fourier harmonic analysis. These components were compared with healthy eyes and the association between each component and best-corrected visual acuity (BCVA) was investigated. Anterior and posterior components increased in both GCD and LCD eyes. Anterior and posterior components of GCD2, anterior of LCD type 1 (LCD1), posterior of LCD type IIIA (LCD 3A), and type IV (LCD4) significantly increased. BCVA was significantly associated with anterior and posterior components in LCD eyes but not in GCD. The anterior components of LCD1, anterior and posterior of LCD3A, and posterior of LCD4 , were positively correlated with BCVA. As conclusions, in GCD eyes, anterior and posterior components differed from those of the control but BCVA was not significantly associated with them. In LCD eyes, the anterior and posterior components increased, and BCVA was significantly associated with the anterior and posterior components., (© 2022. The Author(s).)

Purpose/aim: Detecting keratoconus (KC) progression helps determine the surgical indication for corneal cross-linking (CXL). This retrospective observational study aimed to examine changes in keratometric indices and corneal thickness in patients with KC who used rigid gas-permeable (RGP) contact lenses., Materials and Methods: This study involved 31 eyes (31 patients) diagnosed with KC. No patient had used RGP or any other type of contact lenses for at least 1 month. Corneal topographic data were obtained using three-dimensional anterior segment optical coherence tomography before and after >1 month of RGP lens use., Results: The average and maximum keratometry values changed after using an RGP lens (-1.05 ± 1.92 D, p < 0.01 and -1.65 ± 4.20 D, p = 0.04, respectively); the spherical component of the anterior corneal surface became significantly smaller (p = 0.02). No change was observed in the central or thinnest corneal thickness values. Keratometric changes were greater in eyes with severe KC than in those with moderate KC (p = 0.014)., Conclusions: Keratometry and spherical components of the anterior corneal surface values decreased after RGP lens use; keratometric changes were greater in eyes with severe KC than in those with moderate KC. Corneal progression indices, including corneal thickness, posterior keratometry, and irregular astigmatism values, mostly remained unchanged. It is important to consider these findings when evaluating corneal topography of KC and preparing CXL., Competing Interests: The authors have declared that no competing interests exist.

MyoD, Myf5, myogenin, and MRF4 (also known as Myf6 or herculin) are myogenic regulatory factors (MRFs). MRFs are regarded as master transcription factors that are upregulated during myogenesis and influence stem cells to differentiate into myogenic lineage cells. In this review, we summarize MRFs, their regulatory factors, such as TLE3, NF-κB, and MRF target genes, including non-myogenic genes such as taste receptors. Understanding the function of MRFs and the physiology or pathology of satellite cells will contribute to the development of cell therapy and drug discovery for muscle-related diseases.

Purpose: Accelerated trans-epithelial cross-linking (ATE-CXL), a therapy to halt keratoconus progression, has the merit of widening the indications for thinner corneas (<380 μm). Since a hypotonic solution affects the swollen cornea, corneas of <380 μm thickness at preoperative measurement can be an indication for ATE-CXL. The aim of this retrospective study was to compare the efficacy and safety of ATE-CXL for keratoconus between corneas with thicknesses <380 μm and ≥380 μm., Materials and Methods: Thirty-four eyes of 27 patients who underwent ATE-CXL (30 mW/cm 2 ; 3 minutes) with completion of a 24-month follow-up, were enrolled and divided into two groups: Group 1, thinnest corneal thickness (TCT), <380 μm (n = 10) and Group 2, TCT, ≥380 μm (n = 24). A hypotonic solution was administered to Group 1 until the corneal thickness increased by >380 μm before UV-A irradiation. We measured uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), maximum and average keratometric values (Kmax and AveK), central corneal thickness (CCT), TCT by anterior segment optical coherence tomography, and corneal endothelial cell density (ECD) using specular microscopy. The changes from baseline to 24 months postoperatively between the two groups were compared accordingly., Results: The changes in Kmax and AveK from baseline to 24 months in Group 1 (ΔKmax: -7.8 ± 7.7 D, ΔAveK: -4.3 ± 6.1 D) showed significant decreases compared to those in Group 2 (ΔKmax: 0.2 ± 3.0 D, ΔAveK: 0.6 ± 2.7 D) ( p = .004 and p = .001), and there were no significant changes from baseline to 24 months postoperatively in UCVA, BCVA, CCT, TCT, and ECD in both groups., Conclusion: ATE-CXL is effective and safe for keratoconic corneas in both groups. The effect of reducing keratometric values was greater in the group with thinner corneas.

Objective: To assess the long-term efficacy and safety of accelerated transepithelial corneal cross-linking (ATE-CXL) with 30 mW/cm 2 × 3 min., Methods and Analysis: Thirty-four eyes of 23 patients with progressive keratoconus (KCN) recruited within a single centre were enrolled in this prospective interventional study. Exclusion criteria included: history of Descemet's membrane rupture, glaucoma, uveitis, severe dry eye, concurrent corneal infections, and systemic disease that could affect corneal healing. ATE-CXL was performed with 3 min of ultraviolet-A continuous irradiation (30 mW/cm 2 ). Follow-up examinations were scheduled on postoperative day 1; 1 and 2 weeks; 1, 3 and 6 months; and 1, 2 and 3 years. Main outcome measures were maximum corneal power (Kmax), average corneal power (AvgK), steepest corneal power (Ks), central corneal thickness, thinnest corneal thickness, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA) and endothelial cell density., Results: Mean Kmax, AvgK, Ks, UCVA, BCVA and endothelial cell density did not significantly change over 3 years. The speed of progression obtained by linear regression analysis on corneal parameters (Kmax, AvgK, Ks) improved after ATE-CXL. All baseline parameters correlated with the postoperative Kmax slope. Two eyes underwent ATE-CXL redo because of continued progression after the primary CXL., Conclusion: This is the first report of 3-year results of ATE-CXL with 30 mW/cm 2 × 3 min. ATE-CXL (30 mW/cm 2 × 3 min) was safe and effective for slowing down KCN progression., Trial Registration Number: This study was registered with ID UMIN000009372 in UMIN-Clinical Trials Registry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Myogenic differentiation 1 (Myod1) is involved in the expression of taste receptor type 1 member 1 (Tas1r1) during myogenic differentiation. Further, the target genes of Myod1 participate in transcriptional control, muscle development, and synaptic function. We examined, for the first time, the function of Myod1 in the transcriptional regulation of Tas1r1., Methods: ENCODE chromatin immunoprecipitation and sequencing (ChIP-seq) data of myogenically differentiated C2C12 cells were analyzed to identify the Myod1 and transcription factor 12 (Tcf12) binding sites in the Tas1r1 promoter region. Luciferase reporter assays, DNA affinity precipitation assays, and co-immunoprecipitation assays were also performed to identify the functions of Myod1, Tcf12, and Krüppel-like factor 5 (Klf5)., Results: Based on ENCODE ChIP-seq, Myod1 bound to the Tas1r1 promoter region containing E-boxes 1-3. Luciferase reporter assays revealed that site-directed E-box1 mutations significantly reduced promoter activation induced by Myod1 overexpression. According to the DNA affinity precipitation assay and co-immunoprecipitation assay, Myod1 formed a heterodimer with Tcf12 and bound to E-box1. Further, Klf5 bound to the GT box near E-box1, activating Tas1r1 expression., Conclusions: During myogenic differentiation, the Myod1/Tcf12 heterodimer, in collaboration with Klf5, binds to E-box1 and activates Tas1r1 expression., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2021 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Objective: Cleft palate is among the most frequent congenital defects in humans. While gene-environment multifactorial threshold models have been proposed to explain this cleft palate formation, only a few experimental models have verified this theory. This study aimed to clarify whether gene-environment interaction can cause cleft palate through a combination of specific genetic and environmental factors., Methods: Msx1 heterozygosity in mice ( Msx1 +/- ) was selected as a genetic factor since human MSX1 gene mutations may cause nonsyndromic cleft palate. As an environmental factor, hypoxic stress was induced in pregnant mice by administration of the antiepileptic drug phenytoin, a known arrhythmia inducer, during palatal development from embryonic day (E) 11 to E14. Embryos were dissected at E13 for histological analysis or at E17 for recording of the palatal state., Results: Phenytoin administration downregulated cell proliferation in palatal processes in both wild-type and Msx1 +/- embryos. Bone morphogenetic protein 4 ( Bmp4 ) expression was slightly downregulated in the anterior palatal process of Msx1 +/- embryos. Although Msx1 +/- embryos do not show cleft palate under normal conditions, phenytoin administration induced a significantly higher incidence of cleft palate in Msx1 +/- embryos compared to wild-type littermates., Conclusion: Our data suggest that cleft palate may occur because of the additive effects of Bmp4 downregulation as a result of Msx1 heterozygosity and decreased cell proliferation upon hypoxic stress. Human carriers of MSX1 mutations may have to take more precautions during pregnancy to avoid exposure to environmental risks.

Purpose: We aimed to assess the corneal refractive changes induced by ptosis surgery in patients with acquired ptosis using Fourier harmonic analysis., Methods: This retrospective observational study enrolled consecutive patients who underwent levator aponeurotic surgery for acquired ptosis at the Department of Ophthalmology in the University of Tokyo Hospital from May 2016 to January 2018. Best corrected visual acuity, central corneal thickness, average keratometric corneal power (AvgK), corneal astigmatism, and topographic data using Fourier analysis were analyzed preoperatively and 6 months postoperatively., Results: Thirty-two eyes of 32 patients (age, 72.6 ± 8.5 years) were included in this study. There were no significant differences in best corrected visual acuity and central corneal thickness. However, there were significant decreases in anterior AvgK, anterior corneal astigmatism, and posterior corneal astigmatism 6 months postoperatively (all, P < 0.001). Fourier harmonic analysis showed that the anterior spherical component significantly decreased 6 months postoperatively (P < 0.001). There were no significant differences in other components of the anterior and posterior cornea. There was a significant negative correlation between preoperative posterior AvgK and changes in posterior AvgK (r = -0.891, P < 0.001) and between preoperative posterior corneal astigmatism and changes in posterior corneal astigmatism at 6 months (r = -0.858, P < 0.001)., Conclusions: Anterior and posterior corneal keratometry and posterior corneal astigmatism significantly changed 6 months after ptosis surgery for acquired ptosis.

Mammalian taste bud cells have a limited lifespan and differentiate into type I, II, and III cells from basal cells (type IV cells) (postmitotic precursor cells). However, little is known regarding the cell lineage within taste buds. In this study, we investigated the cell fate of Mash1-positive precursor cells utilizing the Cre-loxP system to explore the differentiation of taste bud cells. We found that Mash1-expressing cells in Ascl1 CreERT2 ::CAG-floxed tdTomato mice differentiated into taste bud cells that expressed aromatic L -amino acid decarboxylase (AADC) and carbonic anhydrase IV (CA4) (type III cell markers), but did not differentiate into most of gustducin (type II cell marker)-positive cells. Additionally, we found that Mash1-expressing cells could differentiate into phospholipase C β2 (PLCβ2)-positive cells, which have a shorter lifespan compared with AADC- and CA4-positive cells. These results suggest that Mash1-positive precursor cells could differentiate into type III cells, but not into most of type II cells, in the taste buds.

To determine the risk factors and unique characteristics of keratoconus (KC) progression after penetrating keratoplasty (PK), anterior segment optical coherence tomography parameters were statistically analyzed in comparison with eyes undergoing PK for other diseases as a control. Ninety-one eyes maintaining clear PK grafts for over 10 years were divided into 2 groups according to the primary indication for PK (KC vs Others groups). Corneal thinning indicators (inferior host thinnest corneal thickness/central corneal thickness [IHT/CCT], inferior graft thinnest corneal thickness/CCT [IGT/CCT]), were smaller whereas anterior chamber depth, and steepest corneal power (Ks), and maximum corneal power (K max ) were larger in the KC group with statistical significance. Graft size, K max and Ks correlated with IHT/CCT and IGT/CCT in the KC group. These correlations were not detected in controls. Graft size and postoperative period were selected by multivariate regression analysis as factors for corneal ectatic changes in the KC group. In conclusion, KC eyes long after PK show inferior graft and host corneal thinning, and corneal protrusion. Corneal power parameters such as K max or Ks can be used to monitor KC progression after PK. A small graft might lead to KC progression after PK.

Objective: The calcineurin-NFAT (nuclear factor for activated T cells)-DSCR (Down syndrome critical region)-1 pathway plays a crucial role as the downstream effector of VEGF (vascular endothelial growth factor)-mediated tumor angiogenesis in endothelial cells. A role for DSCR-1 in different organ microenvironment such as the cornea and its role in ocular diseases is not well understood. Corneal changes can be indicators of various disease states and are easily detected through ocular examinations. Approach and Results: The presentation of a corneal arcus or a corneal opacity due to lipid deposition in the cornea often indicates hyperlipidemia and in most cases, hypercholesterolemia. Although the loss of Apo (apolipoprotein) E has been well characterized and is known to lead to elevated serum cholesterol levels, there are few corneal changes observed in ApoE -/- mice. In this study, we show that the combined loss of ApoE and DSCR-1 leads to a dramatic increase in serum cholesterol levels and severe corneal opacity with complete penetrance. The cornea is normally maintained in an avascular state; however, loss of Dscr-1 is sufficient to induce hyper-inflammatory and -oxidative condition, increased corneal neovascularization, and lymphangiogenesis. Furthermore, immunohistological analysis and genome-wide screening revealed that loss of Dscr-1 in mice triggers increased immune cell infiltration and upregulation of SDF (stromal derived factor)-1 and its receptor, CXCR4 (C-X-C motif chemokine ligand receptor-4), potentiating this signaling axis in the cornea, thereby contributing to pathological corneal angiogenesis and opacity., Conclusions: This study is the first demonstration of the critical role for the endogenous inhibitor of calcineurin, DSCR-1, and pathological corneal angiogenesis in hypercholesterolemia induced corneal opacity.

The aim of this observational study was to examine the characteristics of anterior and posterior corneal topography in keratoconic eyes more than 30 years after penetrating keratoplasty (PK). Patients who maintained clear grafts for more than 30 years after PK were included and divided into the keratoconus (KC) group or other diseases (Others) group, based on the primary indication. Twenty-six eyes of 26 patients were included. The KC group and the Others group included 14 eyes and 12 eyes, respectively. The KC group participants were younger at the time of surgery (P = 0.03). No differences were found in best-spectacle-corrected visual acuity, keratometric power, and central-corneal-thickness. Based on corneal topography using Fourier harmonic analyses, regular astigmatism in the anterior cornea was significantly larger (P = 0.047) and the spherical component in the posterior cornea was significantly lower (P = 0.01) in the KC group. The area under the receiver operating characteristic curve of the spherical component, regular astigmatism, asymmetry component, and higher-order irregularity were 66.07%, 63.10%, 57.14%, and 59.23%, respectively, in the anterior cornea and 80.65%, 52.98%, 63.10%, and 63.99%, respectively, in the posterior cornea. Our results suggested that Fourier harmonic analysis of corneal topography could be useful for patients with KC long after PK.

Purpose: To compare 5-year clinical results of non-Descemet stripping automated endothelial keratoplasty (nDSAEK) and DSAEK., Methods: A retrospective chart review involving patients with non-Fuchs-type bullous keratoplasty who underwent nDSAEK or DSAEK 5 years before the review was performed on demographics, graft survival rate, endothelial cell density (ECD), best-corrected visual acuity (BCVA), and complications., Results: Fifty eyes (nDSAEK 28, DSAEK 22) were included in this study. Common indications for surgery were bullous keratopathy due to glaucoma, cataract surgeries, or laser iridotomy. The graft survival rates in nDSAEK and DSAEK eyes at 1, 3, and 5 years were 0.75 and 0.86, 0.67 and 0.81, and 0.59 and 0.74, respectively. The mean donor ECDs of nDSAEK and DSAEK eyes were 2638 and 2503 cells/mm, respectively; these decreased to 1654 and 1406, 1503 and 1218, and 1108 and 1020 cells/mm at 1, 3, and 5 years, respectively. The mean preoperative BCVAs of nDSAEK and DSAEK eyes were 1.08 and 1.11 LogMAR, respectively; these improved to 0.238 and 0.190, 0.126 and 0.157, and 0.097 and 0.070 LogMAR at 1, 3, and 5 years, respectively. The most common complication was intraocular pressure elevation. There were no statistically significant differences between nDSAEK and DSAEK in graft survival rates, changes in ECD and BCVA, or the occurrence of postoperative complications, with the exception of the change in ECD at 2 years (1173 and 1193 cells/mm, P = 0.0159)., Conclusions: Our 5-year clinical results of nDSAEK and DSAEK did not show significant differences at almost all points.

Mutations in transforming growth factor-beta-induced (TGFBI) gene cause clinically distinct types of corneal dystrophies. To delineate the mechanisms driving these dystrophies, we focused on the R124C mutation in TGFBI that causes lattice corneal dystrophy type1 (LCD1) and generated novel transgenic mice harbouring a single amino acid substitution of arginine 124 with cysteine in TGFBI via ssODN-mediated base-pair substitution using CRISPR/Cas9 technology. Eighty percent of homozygous and 9.1% of heterozygous TGFBI-R124C mice developed a corneal opacity at 40 weeks of age. Hematoxylin and eosin and Masson trichrome staining showed eosinophilic deposits in subepithelial corneal stroma that stained negative for Congo-red. Although amyloid deposition was not observed in TGFBI-R124C mice, irregular amorphous deposits were clearly observed via transmission electron microscopy near the basement membrane. Interestingly, we found that the corneal deposition of TGFBI protein (TGFBIp) was significantly increased in homozygous TGFBI-R124C mice, suggesting a pathogenic role for the mutant protein accumulation. Furthermore, as observed in the LCD1 patients, corneal epithelial wound healing was significantly delayed in TGFBI-R124C mice. In conclusion, our novel mouse model of TGFBI-R124C corneal dystrophy reproduces features of the human disease. This mouse model will help delineate the pathogenic mechanisms of human corneal dystrophy.

Objective: Pain control is imperative in orthodontic treatment. Adenosine triphosphate (ATP) is a key mediator released from periodontal ligament cells that excites nociceptive nerve endings. Vesicular nucleotide transporter (VNUT), encoded by the Solute carrier family 17 member 9 (SLC17A9) gene, participates in ATP uptake into secretory vesicles; thus, it may mediate tooth movement-induced pain. In the present study, we examined whether VNUT in periodontal ligament cells participates in tooth movement-induced nociception., Design: Expression levels of SLC17A9, connexin 43, and pannexin 1 in human periodontal ligament fibroblasts (HPDLFs) were examined by quantitative reverse transcription-polymerase chain reaction. Mechanical force via centrifugation-induced ATP release was measured using an ATP bioluminescence assay. Inhibitors were used to evaluate the role of ATP transporters. Face-grooming behaviors were assessed as indicators of nociceptive responses after experimental tooth movement in rats, as well as the effects of drugs for the pain-like behavior., Results: After HPDLFs underwent mechanical stimulation by centrifugation, SLC17A9 mRNA expression in the cells was significantly upregulated. Increased ATP release from HPDLFs after mechanical stimulation was suppressed by treatment with clodronic acid, a VNUT inhibitor, at concentrations of 0.1 and 1.0 μM. In rats, face-grooming behaviors (indicators of nociception) were significantly increased on day 1 after experimental tooth movement. Increased face-grooming behaviors were suppressed by systemic administration of clodronic acid (0.1 mg/kg)., Conclusions: These results indicate that release of ATP from periodontal ligament cells via VNUT is important for nociceptive transduction during orthodontic treatment. Thus, VNUT may provide a novel drug target for tooth movement-induced pain., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Studies on the penetration of orally administered cephalosporins to the aqueous humor are scarce. Therefore, in this study, we determined the concentration of cefcapene, a third-generation cephalosporin administrated orally as pivalate ester (cefcapene pivoxil), in the aqueous humor of patients undergoing cataract surgery to assess its potential for preventing postoperative endophthalmitis., Methods: Forty-four patients were administered a single dose of 100 mg cefcapene pivoxil preoperatively. Blood and aqueous humor samples were obtained at the time of surgery, and cefcapene concentrations were measured using ultra-performance liquid chromatography with tandem mass spectrometric detection., Results: The samples were obtained from 41 eyes of 39 patients (two patients underwent surgery in both eyes). The median cefcapene concentrations in the aqueous humor after 1-2 h, 2-3 h, and later than 3 h were 8.3, 18.4, and 23.7 ng/mL, respectively. The median cefcapene concentrations in serum after 1-2 h, 2-3 h, and later than 3 h were 198.5, 287.2, and 170.3 ng/mL, respectively. Aqueous humor penetration of cefcapene after 1-2 h, 2-3 h, and later than 3 h was 4.1, 7.9, and 13.5% respectively., Conclusions: Aqueous humor penetration of orally-administered cefcapene pivoxil in patients undergoing cataract surgery was poor. Therefore, cefcapene pivoxil was unlikely to be effective for preventing endophthalmitis after cataract surgery., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Inflammation plays an important role in pathological angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation; however, a comprehensive description of its role in angiogenesis remains elusive. Here, we show that RIP1 is abundantly expressed in infiltrating macrophages during angiogenesis, and genetic or pharmacological inhibition of RIP1 kinase activity using kinase-inactive RIP1 K45A/K45A mice or necrostatin-1 attenuates angiogenesis in laser-induced choroidal neovascularization, Matrigel plug angiogenesis, and alkali injury-induced corneal neovascularization in mice. The inhibitory effect on angiogenesis is mediated by caspase activation through a kinase-independent function of RIP1 and RIP3. Mechanistically, infiltrating macrophages are the key target of RIP1 kinase inhibition to attenuate pathological angiogenesis. Inhibition of RIP1 kinase activity is associated with caspase activation in infiltrating macrophages and decreased expression of proangiogenic M2-like markers but not M1-like markers. Similarly, in vitro, catalytic inhibition of RIP1 down-regulates the expression of M2-like markers in interleukin-4-activated bone marrow-derived macrophages, and this effect is blocked by simultaneous caspase inhibition. Collectively, these results demonstrate a nonnecrotic function of RIP1 kinase activity and suggest that RIP1-mediated modulation of macrophage activation may be a therapeutic target of pathological angiogenesis., Competing Interests: The authors declare no competing interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Purpose: To compare the clinical characteristics of acute hydrops between eyes with recurrent keratoconus and eyes with treatment-naïve keratoconus. Methods: Six eyes with acute hydrops caused by recurrent keratoconus (recurrent group) and 29 eyes with acute hydrops due to treatment-naïve keratoconus (naïve group) were included. We collected data from anterior-segment optical coherence tomography (AS-OCT), corneal topography and medical records. With AS-OCT, we investigated the location of Descemet's membrane break, the length and frequency of Descemet's membrane detachment, and the speed of corneal thinning before acute hydrops. Results: Descemet's membrane breaks were detectable in 6 cases in the recurrent group (100%) and 7 cases in the naïve group (70%). Distance from the break to the central line was 2-3 mm in the recurrent group, and less than 1 mm in the naïve group ( p < .001). Detachment length was significantly greater in the recurrent group than in the naïve group ( p = .003). Steep corneal power values tended to increase before acute hydrops in the recurrent group, but the difference between groups was not significant (observation period; 6.03 ± 2.67, 7.36 ± 5.53 years, respectively). Penetrating keratoplasty was required in 5 cases (83%) in the recurrent group, and 8 cases (28%) in the naïve group ( p = .02). Conclusions: Acute hydrops due to recurrent keratoconus occurred around graft-host junctions and was more severe than that in eyes with treatment-naïve keratoconus. Severity assessment of Descemet's membrane detachment using AS-OCT provided clues not only for diagnosis, but also for predicting prognosis.

Nanoparticles are used in industry and medicine, because of their physiochemical properties, such as size, charge, large surface area and surface reactivity. Recently, metal nanoparticles were reported to show cell toxicity on cancer cells. In this study, we focused novel platinum nanoparticles-conjugated latex beads (P2VPs), platinum nanocomposite (PtNCP) beads, and investigated the possibility to incorporate novel anti-cancer effect of these combined nanoparticles. Oral squamous cell carcinoma cell lines, HSC-3-M3 cells were injected subcutaneously into the back of nude mice to produce a xenograft model. PtNCP beads were injected locally and examined by measuring tumor volume and comparing pathological histology. PtNCP beads treatment suppressed tumor growth and identified increasing pathological necrotic areas, in vivo. PtNCP beads inhibited the cell viability of HSC-3-M3 cells in dose-dependent manner and induced the cytotoxicity with extracellular LDH value, in vitro. Furthermore, SEM images were morphologically observed in PtNCP beads-treated HSC-3-M3 cells. The aggregation of the PtNCP beads on the cell membrane, the destructions of the cell membrane and globular structures were observed in the SEM image. Our results indicated that a potential anti-cancer effect of the PtNCP beads, suggesting the possibility as a therapeutic tool for cancer cell-targeted therapy. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2281-2287, 2019., (© 2019 Wiley Periodicals, Inc.)