The Necroptosis Pathway Is Upregulated in the Cornea in Mice With Ocular Graft-Versus-Host Disease.

Purpose: To identify molecular signatures specific for ocular graft-versus-host disease (GVHD) by proteomic analysis of corneas from mice with GVHD. Methods: We identified differentially expressed proteins (DEPs) in corneal samples from GVHD model mice and syngeneic control mice 4 weeks after bone marrow transplantation. Data-independent acquisition analysis was performed on individual samples, and the roles of DEPs in biological pathways related to GVHD were evaluated via bioinformatics and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Three important signaling pathways were upregulated in the cornea in mice with GVHD: (1) the necroptosis pathway, (2) the mitogen-activated protein kinase (MAPK) pathway, and (3) as previously reported, the neutrophil extracellular trap (NET) pathway. In those signaling pathways, we identified new upregulated molecules, including (1) receptor-interacting protein kinase 1 (RIPK1), RIPK3, interferon regulatory factor 9, the interferon-induced double-stranded RNA-activated protein kinase lipoxygenase, and high mobility group box1 (HMGB1) which are damage-associated molecular patterns (DAMPs) in the necroptosis pathway; (2) the sequentially upregulated interleukin 1 (IL-1) receptor-associated kinase (IRAK), an evolutionarily conserved signaling intermediate in the Toll pathway (ECSIT), and p38, which is downstream of the IL-1 receptor and increased CDC42/Rac (Rac2), a Rho family GTPase in the MAPK pathway; and (3) the integrin components CR3 and macrophage-1 antigen (MAC-1), which are DAMPs, and the pyroptosis-related protein gasdermin D (GSDMD) in the NET pathway. Conclusions: These novel molecules may help researchers elucidate the pathogenesis of GVHD and identify new therapeutic targets for corneal changes in patients with ocular GVHD.

Mitochondrial control of hypoxia-induced pathological retinal angiogenesis.

OBJECTIVE: Pathological retinal neovascularization is vision-threatening. In mouse oxygen-induced retinopathy (OIR) we sought to define mitochondrial respiration changes longitudinally during hyperoxia-induced vessel loss and hypoxia-induced neovascularization, and to test interventions addressing those changes to prevent neovascularization. METHODS: OIR was induced in C57BL/6J mice and retinal vasculature was examined at maximum neovessel formation. We assessed total proteome changes and the ratio of mitochondrial to nuclear DNA copy numbers (mtDNA/nDNA) of OIR vs. control retinas, and mitochondrial oxygen consumption rates (OCR) in ex vivo OIR vs. control retinas (BaroFuse). Pyruvate vs. vehicle control was supplemented to OIR mice either prior to or during neovessel formation. RESULTS: In OIR vs. control retinas, global proteomics showed decreased retinal mitochondrial respiration at peak neovascularization. OCR and mtDNA/nDNA were also decreased at peak neovascularization suggesting impaired mitochondrial respiration. In vivo pyruvate administration during but not prior to neovessel formation (in line with mitochondrial activity time course) suppressed NV. CONCLUSIONS: Mitochondrial energetics were suppressed during retinal NV in OIR. Appropriately timed supplementation of pyruvate may be a novel approach in neovascular retinal diseases.

Choroidal thinning in myopia is associated with axial elongation and severity of myopic maculopathy.

High myopia can lead to pathologic myopia and visual impairment, whereas its causes are unclear. We retrospectively researched high myopia cases from patient records to investigate the association between axial elongation and myopic maculopathy. Sixty-four eyes were examined in patients who visited the department between July 2017 and June 2018, had an axial length of 26 mm or more, underwent fundus photography, and had their axial length measured twice or more. The average axial length was 28.29 ± 1.69 mm (mean ± standard deviation). The average age was 58.3 ± 14.4 years old. Myopic maculopathy was categorized as mild (grades 0 and 1) and severe (grades 2, 3, and 4). The severe group had longer axial lengths than the mild group (P < 0.05). Moreover, the severe group exhibited thinner choroidal thickness than the mild group (P < 0.05). When subjects were grouped by axial elongation over median value within a year, the elongation group showed thinner central choroidal thickness than the non-elongation group (142.1 ± 91.9 vs. 82.9 ± 69.8, P < 0.05). In conclusion, in patients with high myopia, the severity of maculopathy correlated with choroidal thickness and axial length. Thinner choroidal thickness was associated with axial elongation based on the baseline axial length.

Establishment of an in vitro choroid complex system for vascular response screening.

The choroid, a vascularized tissue situated between the retina and the sclera, plays a crucial role in maintaining ocular homeostasis. Despite its significance, research on choroidal abnormalities and the establishment of effective in vitro models have been limited. In this study, we developed an in vitro choroid model through the co-culture of human induced pluripotent stem cells (hiPSC)-derived endothelial cells (ECs) and mouse choroidal fibroblasts (msCFs) with hiPSC-derived retinal pigment epithelial (RPE) cells via a permeable membrane. This model, inclusive of ECs, CFs, and RPE cells, exhibited similarities with in vivo choroidal vessels, as confirmed through immunohistochemistry of extracellular matrix markers and vascular-related markers, as well as choroid angiogenesis sprouting assay analysis. The effectiveness of our in vitro model was demonstrated in assessing vascular changes induced by drugs targeting vasoregulation. Our model offers a valuable tool for gaining insights into the pathological mechanisms underlying choroid development and the progression of choroidal vascular diseases.

Inhibition of hypoxia-inducible factors suppresses subretinal fibrosis.

Age-related macular degeneration (AMD) is a common cause of vision loss. The aggressive form of AMD is associated with ocular neovascularization and subretinal fibrosis, representing a responsive outcome against neovascularization mediated by epithelial-mesenchymal transition of retinal pigment epithelium (RPE) cells. A failure of the current treatment (anti-vascular endothelial growth factor therapy) has also been attributed to the progression of subretinal fibrosis. Hypoxia-inducible factors (HIFs) increase gene expressions to promote fibrosis and neovascularization. HIFs act as a central pathway in the pathogenesis of AMD. HIF inhibitors may suppress ocular neovascularization. Nonetheless, further investigation is required to unravel the aspects of subretinal fibrosis. In this study, we used RPE-specific HIFs or von Hippel-Lindau (VHL, a regulator of HIFs) conditional knockout (cKO) mice, along with pharmacological HIF inhibitors, to demonstrate the suppression of subretinal fibrosis. Fibrosis was suppressed by treatments of HIF inhibitors, and similar suppressive effects were detected in RPE-specific Hif1a/Hif2a- and Hif1a-cKO mice. Promotive effects were observed in RPE-specific Vhl-cKO mice, where fibrosis-mediated pathologic processes were evident. Marine products' extracts and their component taurine suppressed fibrosis as HIF inhibitors. Our study shows critical roles of HIFs in the progression of fibrosis, linking them to the potential development of therapeutics for AMD.

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.

A Possible Reciprocal Relationship Between Myopia and Dry Eye Disease in Japanese Teenagers.

Purpose: To investigate the relationship between dry eye disease (DED) and myopia in Japanese teenagers. Methods: This clinic-based, retrospective, cross-sectional study assessed DED condition in 10- to 19-year-old teenagers presenting at Japanese eye clinics. They included 106 high myopic patients (HM; mean age, 16.4 ± 2.2 years), 494 mild myopic patients (15.0 ± 2.6 years) and 82 non-myopic teenagers (NM; 13.8 ± 2.6 years). Subjective refraction and anisometropia were measured. Myopia grade was classified as HM (≤ -6.00 D), MM (> -6.00 D, < -0.50 D), or NM (≥ -0.5 D). The presence of DED-related symptoms including dryness, irritation, pain, fatigue, blurring and photophobia were assessed through a questionnaire. Tear film break-up time (BUT) and fluorescein corneal staining were investigated. Comparison among three groups and regression analysis of myopic error and other variables were conducted. Results: Anisometropia and astigmatic error were greatest in the HM group compared with the other groups (p < 0.001). The HM group reported less photophobia (p < 0.001) and less pain (p = 0.039) compared with the NM group. Regression analysis revealed that myopic error was correlated with astigmatic error (ß = -0.231, p <0.001), anisometropia (ß = -0.191, p <0.001), short BUT (ß = -0.086, p = 0.028) and the presence of diagnosed DED (ß = -0.112, p = 0.003). Dryness (ß = -0.127 p = 0.004), photophobia (ß = 0.117, p = 0.002) and pain (ß = 0.084, p = 0.034) correlated with myopic error. Conclusion: This study associated clinical findings of DED in HM teenagers. The present results suggest DED might be associated with myopia, possibly in a reciprocal relationship.

Slowing of Greater Axial Length Elongation Stemming from the Coronavirus Disease 2019 Pandemic with Increasing Time Outdoors: The Tokyo Myopia Study.

Purpose: To investigate the changes in axial length (AL) elongation and other ocular parameters before and during the coronavirus disease 2019 pandemic. Design: A longitudinal school-based study. Participants: Public elementary schoolchildren in Tokyo (grades 1-6; age, 6-12 years) participated in this study from 2018 to 2021. Methods: All participants underwent eye examinations and provided written consent to measurements of the noncycloplegic refraction and ocular biometry including AL, among others. The students' parents also completed a questionnaire about the students' lifestyles. We included the right eye in our analysis and compared the changes in the ocular parameters among the periods using a linear mixed-effects model for repeated measures and examined the univariate and step-wise multiple regression analyses to evaluate the associations between myopia and other covariates. Main Outcome Measures: Changes in AL elongation and other ocular parameters from 2018 to 2019 (prepandemic), that of 2019 to 2020 (immediately after the pandemic onset), and that of 2020 to 2021 (during the pandemic). Results: A total of 578 students before the pandemic period, 432 immediately after the pandemic onset, and 457 during the pandemic period were evaluated. The changes in the ALs and spherical equivalents (SEs) a year before, immediately after onset, and during the pandemic were 0.31 mm/-0.20 diopter, 0.38 mm/-0.27 diopter, and 0.28 mm/-0.47 diopter, respectively (ALs, P < 0.001; SEs, P = 0.014). The results of the questionnaire showed that time spent outdoors daily had changed during the 3 years to 79, 63, and 77 minutes/day, respectively (P < 0.001). Time spent using smartphones or tablets increased year by year to 41, 52, and 62 minutes/day (P < 0.001). The greatest AL elongation occurred during the period when the shortest amount of time was spent outdoors during the 3 years. Conclusions: These results suggested that the school closures and decreasing time spent outdoors might have caused greater AL elongation among schoolchildren in Tokyo; however, it is possible that, although the time spent in near work still increased, the return to the time spent outdoors to the prepandemic levels may have affected the slowing of AL elongation after lockdown. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of Eyelid Hygiene on Functional Visual Acuity After Cataract Surgery: A Randomized Controlled Study.

Purpose: To evaluate the effect of eyelid hygiene after cataract surgery on eyelid and ocular surface findings, subjective symptoms and visual function, including functional visual acuity (FVA) and higher order aberration, in a randomized controlled study. Methods: Fifty patients who underwent cataract surgery at a single institution were involved. Twenty-five patients were instructed to wipe their eyelids twice a day from one to four weeks postoperatively, whereas the other 25 patients did not perform any eyelid hygiene. Optical measurement, FVA, meibomian glands, the grade of meibum, lid margin findings, fluorescein corneal staining findings, dry eye-related subjective symptoms and surgical satisfaction were assessed both preoperatively and one month postoperatively. Results: In the eyelid hygiene group, the visual maintenance ratio of FVA improved significantly (p = 0.048) and the higher order aberration of the 4th + 6th order deteriorated less (p = 0.027) compared with the control group. Multiple regression analyses showed that the change in visual maintenance ratio was associated with surgical satisfaction (p = 0.003), change in corneal staining score (p = 0.007), history of eye diseases (p = 0.029) and eyelid hygiene (p = 0.048). Conclusions: Eyelid hygiene after cataract surgery may be effective for visual function measured with an FVA test.

Myopia Is an Ischemic Eye Condition: A Review from the Perspective of Choroidal Blood Flow.

Myopia is a common refractive error that affects a large proportion of the population. Recent studies have revealed that alterations in choroidal thickness (ChT) and choroidal blood flow (ChBF) play important roles in the progression of myopia. Reduced ChBF could affect scleral cellular matrix remodeling, which leads to axial elongation and further myopia progression. As ChT and ChBF could be used as potential biomarkers for the progression of myopia, several recent myopia treatments have targeted alterations in ChT and ChBF. Our review provides a comprehensive overview of the recent literature review on the relationship between ChBF and myopia. We also highlight the importance of ChT and ChBF in the progression of myopia and the potential of ChT as an important biomarker for myopia progression. This summary has significant implications for the development of novel strategies for preventing and treating myopia.

Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response.

Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen.

Deep learning segmentation of non-perfusion area from color fundus images and AI-generated fluorescein angiography.

The non-perfusion area (NPA) of the retina is an important indicator in the visual prognosis of patients with branch retinal vein occlusion (BRVO). However, the current evaluation method of NPA, fluorescein angiography (FA), is invasive and burdensome. In this study, we examined the use of deep learning models for detecting NPA in color fundus images, bypassing the need for FA, and we also investigated the utility of synthetic FA generated from color fundus images. The models were evaluated using the Dice score and Monte Carlo dropout uncertainty. We retrospectively collected 403 sets of color fundus and FA images from 319 BRVO patients. We trained three deep learning models on FA, color fundus images, and synthetic FA. As a result, though the FA model achieved the highest score, the other two models also performed comparably. We found no statistical significance in median Dice scores between the models. However, the color fundus model showed significantly higher uncertainty than the other models (p < 0.05). In conclusion, deep learning models can detect NPAs from color fundus images with reasonable accuracy, though with somewhat less prediction stability. Synthetic FA stabilizes the prediction and reduces misleading uncertainty estimates by enhancing image quality.

Meningeal Carcinomatosis Presenting with Bilateral Loss of Vision.

Meningeal carcinomatosis (MC) has an extremely poor prognosis and can present with various neurological symptoms. A 68-year-old man presented to our hospital with a 1 month history of headache and nausea followed by sudden decrease in vision in both eyes. Whilst being examined in the ophthalmology department he lost consciousness and had a generalised tonic clonic seizure. Accordingly, he was transferred to the Emergency Department. Head magnetic resonance imaging showed hydrocephalus. Abdominal contrast-enhanced computed tomography scanning reported changes suggestive of gastric carcinoma. Cerebrospinal fluid cytological examination showed numerous atypical cells, leading to the diagnosis of MC. An upper gastrointestinal endoscopy revealed an advanced gastric tumour. Systemic chemotherapy was initiated, however, he died within 16 days of admission. At autopsy, poorly differentiated adenocarcinoma was identified in the subarachnoid space, however it had not invaded the brain parenchyma or optic chiasm. This is the first report of loss of vision being the first presenting symptom of new-onset gastric carcinoma with MC. Although rare, MC should be suspected in cases where patients present with sudden loss of vision and symptoms of meningeal irritation, where there are no ophthalmological findings to explain the vision loss.

Retinal ischemic diseases and promising therapeutic molecular targets.

Retinal ischemia is a fundamental pathologic condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, age-related macular degeneration, and other eye diseases. Extensive inflammation, redox imbalance, apoptosis, and abnormal vascular formation in retinal ischemia could lead to visual impairments. Developing or finding effective treatments is urgently needed to protect the eye against retinal ischemia and related damage. To address the demand, we have searched for promising therapeutic molecular targets in the eye (e.g., hypoxia-inducible factor [HIF], peroxisome proliferator-activated receptor-alpha [PPARα], and nicotinamide adenine dinucleotide [NAD+]), and found that modulations of each molecular target might protect the eye against retinal ischemic damage in terms of complex pathologic mechanisms. In the current article, we review and update the therapeutic evidence of modulation of HIF, PPARα, or NAD+ and discuss future directions for developing promising drugs based on these molecular targets. This summary urges research to obtain more solid evidence of each molecular target in retinal ischemic diseases.

Symptomatic Presbyopia may Develop Earlier in Patients With Glaucoma-A Cross-Sectional Retrospective Cohort Study.

Purpose: The purpose of this study was to explore risk factors for symptomatic presbyopia, defined as near add power ≥1.50 diopters, in patients with glaucoma. Methods: Treated glaucoma (n = 56), untreated glaucoma (n = 21), and control individuals (n = 376), aged 40 to 55 years at first visit, were enrolled in the study, and near add power, retinal thickness, and visual field were examined. The association between near add power and ocular parameters and the odds ratios (ORs) for symptomatic presbyopia were investigated. Survival analysis for symptomatic presbyopia was conducted. Results: Age, astigmatic power, mean deviation, and ganglion cell complex thickness were associated with near add power. The OR for symptomatic presbyopia was significant for age (OR = 1.51), astigmatism (OR = 1.01), mean deviation (OR = 0.72), ganglion cell complex thickness (OR = 0.98), treated and untreated glaucoma (OR = 2.09), and use of glaucoma eye drops (OR = 3.33). Survival analysis showed that the treated glaucoma group reached the near add power endpoint of ≥1.50 D (symptomatic presbyopia) significantly earlier than the other two groups, and there was no difference between the control and untreated glaucoma groups. Conclusions: Glaucoma patients treated with eye drops may start near correction earlier. Translational Relevance: Symptomatic presbyopia may develop earlier in patients with glaucoma, and our findings could further contribute to better management and understanding of presbyopia with glaucoma.

Halofuginone prevents outer retinal degeneration in a mouse model of light-induced retinopathy.

Photoreceptor cell death can cause progressive and irreversible visual impairments. Still, effective therapies on retinal neuroprotection are not available. Hypoxia-inducible factors (HIFs) are transcriptional factors which strongly regulate angiogenesis, erythropoiesis, intracellular metabolism, and programed cell death under a hypoxic or an abnormal metabolic oxidative stress condition. Therefore, we aimed to unravel that inhibition of HIFs could prevent disease progression in photoreceptor cell death, as recent studies showed that HIFs might be pathologic factors in retinal diseases. Adult male balb/cAJcl (8 weeks old; BALB/c) were used to investigate preventive effects of a novel HIF inhibitor halofuginone (HF) on a murine model of light-induced retinopathy. After intraperitoneal injections of phosphate-buffered saline (PBS) or HF (0.4 mg/kg in PBS) for 5 days, male BALB/c mice were subjected to a dark-adaption to being exposed to a white LED light source at an intensity of 3,000 lux for 1 hour in order to induce light-induced retinal damage. After extensive light exposure, retinal damage was evaluated using electroretinography (ERG), optical coherence tomography (OCT), and TUNEL assay. Light-induced retinal dysfunction was suppressed by HF administration. The amplitudes of scotopic a-wave and b-wave as well as that of photopic b-wave were preserved in the HF-administered retina. Outer retinal thinning after extensive light exposure was suppressed by HF administration. Based on the TUNEL assay, cell death in the outer retina was seen after light exposure. However, its cell death was not detected in the HF-administered retina. Halofuginone was found to exert preventive effects on light-induced outer retinal cell death.

Cellular senescence promotes meibomian gland dysfunction in a chronic graft-versus-host disease mouse model.

PURPOSE: Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. METHODS: A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. RESULTS: Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. CONCLUSIONS: Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.

Ten-year outcomes of congenital cataract surgery performed within the first six months of life.

PURPOSE: To investigate the long-term outcomes of congenital cataract surgery performed within the first 6 months of life. SETTING: 11 ophthalmic surgical sites in Japan. DESIGN: Retrospective chart review. METHODS: Medical charts were retrospectively reviewed for 216 eyes of 121 patients. The age at surgery was 2.9 ± 1.7 months, with follow-up duration 13.0 ± 2.3 years. The cohort consisted of 83 cases with bilateral aphakia, 12 with bilateral pseudophakia, 20 with unilateral aphakia, and 6 with unilateral pseudophakia. RESULTS: Surgical intervention within the critical period of visual system development (10 weeks for bilateral and 6 weeks for unilateral cases) led to significantly better final visual acuity than surgery conducted after this time frame. The incidence of secondary glaucoma was similar between groups while the occurrence of visual axis opacification was more frequent with earlier surgery. A forward stepwise multiple regression analysis revealed that the final visual acuity was significantly associated with laterality of cataract (better outcomes in bilateral cases), phakic status (with pseudophakia outperforming aphakia), presence of systemic and ocular comorbidities, and development of secondary glaucoma. Secondary glaucoma was significantly more prevalent in aphakic eyes than pseudophakic eyes. CONCLUSIONS: In patients with genuine congenital cataract, surgery within the critical period of visual development results in better final visual acuity, albeit with an increased risk of visual axis opacification. The use of IOL with sophisticated surgical techniques shows promise even in congenital cataract surgery.

Relation between a history of glaucoma and subjective happiness: the JPHC-Next study.

OBJECTIVE: This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness. METHODS AND ANALYSIS: We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40-74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs. RESULTS: Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40-59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88). CONCLUSIONS: These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men.

Scleral remodeling during myopia development in mice eyes: a potential role of thrombospondin-1.

BACKGROUND: Scleral extracellular matrix (ECM) remodeling plays a crucial role in the development of myopia, particularly in ocular axial elongation. Thrombospondin-1 (THBS1), also known as TSP-1, is a significant cellular protein involved in matrix remodeling in various tissues. However, the specific role of THBS1 in myopia development remains unclear. METHOD: We employed the HumanNet database to predict genes related to myopic sclera remodeling, followed by screening and visualization of the predicted genes using bioinformatics tools. To investigate the potential target gene Thbs1, we utilized lens-induced myopia models in male C57BL/6J mice and performed Western blot analysis to detect the expression level of scleral THBS1 during myopia development. Additionally, we evaluated the effects of scleral THBS1 knockdown on myopia development through AAV sub-Tenon's injection. The refractive status and axial length were measured using a refractometer and SD-OCT system. RESULTS: During lens-induced myopia, THBS1 protein expression in the sclera was downregulated, particularly in the early stages of myopia induction. Moreover, the mice in the THBS1 knockdown group exhibited alterations in myopia development in both refraction and axial length changed compared to the control group. Western blotting analysis confirmed the effectiveness of AAV-mediated knockdown, demonstrating a decrease in COLA1 expression and an increase in MMP9 levels in the sclera. CONCLUSION: Our findings indicate that sclera THBS1 levels decreased during myopia development and subsequent THBS1 knockdown showed a decrease in scleral COLA1 expression. Taken together, these results suggest that THBS1 plays a role in maintaining the homeostasis of scleral extracellular matrix, and the reduction of THBS1 may promote the remodeling process and then affect ocular axial elongation during myopia progression.