GGT1 Suppresses the Development of Ferroptosis and Autophagy in Mouse Retinal Ganglion Cell Through Targeting GCLC.

Background: Glaucoma is a neurodegenerative disorder characterized with optic nerve injury and the loss of retinal ganglion cells (RGCs). Ferroptosis has been proved to be associated with the degradation of RGCs. The aim of this study is to elucidate the relationship between ferroptosis and glaucoma pathogenesis, and unveil the underlying mechanism. Methods: Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of RGCs. The accumulation of cellular iron was measured by Iron assay kit, and the level of reactive oxygen species (ROS) was detected by fluorescence probe. The mitochondrial morphology and autophagosomes were analysed by using transmission electron microscopy (TEM). The contents of glutathione (GSH) and malondialdehyde (MDA) were tested by a GSH assay kit and an MDA detection kit, respectively. The expression of autophagy-related proteins was detected by Western blotting. Results: A serious cell damage, aberrant iron homeostasis, and oxidative stress was shown in RGC-5 after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and gamma-Glutamyl transpeptidase 1 (GGT1) knockdown, but these effects were significantly alleviated by overexpression of GGT1 or ferroptosis inhibitors. The TEM and immunofluorescent results indicated that mitochondria impairment and autophagosome accumulation in OGD/R-treated cells was improved after GGT1 overexpression, while the phenomenon in GGT1-silenced cells was aggravated. Furthermore, we found that GGT1 can interact with glutamate cysteine ligase catalytic subunit (GCLC) to inhibit autophagy and ferroptosis in RGC-5 cells. Conclusion: GGT1 represses autophagy in RGC-5 cells by targeting GCLC, which further restrains the development of ferroptosis in cells.

Fruit and vegetable intake and the risk of cataract: insights from the UK Biobank study.

PURPOSE: A prospective cohort study to investigate the association between fruit and vegetable (F&V) intake and the risk of cataract. METHODS: We included 72,160 participants who were free of cataract at baseline from the UK Biobank. Frequency and type of F&V intake were assessed using a web-based 24 h dietary questionnaire from 2009 to 2012. Development of cataract during the follow-up was defined by self-report or hospital inpatient records up to 2021. Cox proportional regression models were used to estimate the association between F&V intake and incident cataract. RESULTS: During a mean follow-up of 9.1 years, 5753 participants developed cataract with a corresponding incidence of 8.0%. After adjusting for multiple demographic, medical and lifestyle covariates, higher intake of F&V were associated with a lower risk of cataract (≥6.5 vs. <2 servings/week: hazards ratio [HR]: 0.82, 95% CI: 0.76 to 0.89; P < 0.0001). Regarding specific types, significant reduced risk of cataract was found for higher intake of legumes (P = 0.0016), tomatoes (≥5.2 vs. <1.8 servings/week: HR: 0.94, 95% CI: 0.88 to 1.00), and apple and pear (>7 vs. <3.5 servings/week: 0.89, 95% CI: 0.83 to 0.94; P < 0.0001), but not for cruciferous vegetables, green leafy vegetables, berry, citrus fruit or melon. Smokers were found to benefit more from F&V intake than former and never smokers. Men also could benefit more from higher vegetable intake than women. CONCLUSIONS: More F&V intake, especially legumes, tomatoes, apple, and pear, was associated with a lower risk of cataract in this UK Biobank cohort.

Evaluation of Systemic Medications Associated With Surgically Treated Cataract Among US Adults.

PURPOSE: To comprehensively determine the associations between systemic medications and surgically treated cataract in the US population. DESIGNS: Retrospective cross-sectional study. METHODS: Participants aged ≥40 years from the 1999-2008 National Health and Nutrition Examination Survey (NHANES) were included. Surgically treated cataract was defined as cataract requiring a procedure. Data on prescription drug use over the past 30 days were collected via home interviews. Drug categories for ophthalmic indications and those prescribed in less than 0.5% of the participants were excluded from the analysis. Separate logistic regression models were used to explore associations between each drug category and surgically treated cataract. The Benjamin-Hochberg procedure was used to control the false discovery rate. RESULTS: A total of 14,931 were included in the present analysis. The weighted prevalence of surgically treated cataract was 9.6% (n=2010). We identified 20 drug categories that had significant associations with surgically treated cataract, of which 8 associations remained statistically significant after further adjustment for pertinent comorbidities. The 3 drug categories with the highest odds ratio (OR) values were tricyclic antidepressants (OR, 2.21; 95% CI, 1.38-3.51; P = .001), insulin (OR, 2.13; 95% CI, 1.48-3.07; P = 9.41×10-5) and group III antiarrhythmic agents (OR, 2.00; 95% CI, 1.25-3.19; P = .004). The use of sex hormone combinations among women reduced the risk of having surgically treated cataract (OR, 0.011; 95% CI, 0.001-0.089; P = 5.98×10-5). Dose-response relationships were observed for all 8 drug categories. CONCLUSIONS: Our comprehensive evaluation provides new knowledge on the complex relationships between systemic medications and surgically treated cataract.

Comparison of the effectiveness and safety of travoprost and latanoprost for the management of open-angle glaucoma given as an evening dose.

As intraocular pressure (IOP) is primarily higher in the morning, an evening dose of prostaglandin analogs is typically used as monotherapy to decrease IOP in patients with open-angle glaucoma. Travoprost (TV) has reported efficacy in treating open-angle glaucoma; however, the safety and efficacy may be different compared with that for latanoprost (LT). The aim of the present study was to compare the effectiveness and safety of an evening dose of TV compared with that of LT in treating open-angle glaucoma. Data including IOP, results of lid and slit-lamp examination and ophthalmoscopy, as well as adverse effects in 250 affected eyes from patients with open-angle glaucoma who received either TV (n=89) or LT (n=161) once in the evening for 3-months were included in the analyses. At the end of treatment, TV (23.45±1.52 vs. 19.15±1.01 mmHg; P<0.0001) and LT (23.93±2.11 vs. 19.45±1.11 mmHg; P<0.0001) successfully lowered the IOP. In addition, there was no significant difference in the reduction of IOP values at the end of treatment between the two groups (P=0.120). Furthermore, there were no adverse effects on visual acuity (P>0.05), except for non-visual acuity, for example hyperemia (P<0.0001 for both groups), while there was a significant increase in the number of patients with dry eyes receiving TV (P=0.020) and a significant increase with eyelid swelling (P=0.036) and headache (P=0.037) in patients receiving LT. In conclusion, evening doses of TV and LT had the same efficacy and manageable adverse effects in the treatment of open-angle glaucoma (level of evidence, 3).