Retinal ganglion cells (RGCs), the projection neurons of the eye, are irreversibly lost once the optic nerve is injured, which is a critical mechanism of glaucoma. Mobile zinc (Zn2+) levels rapidly increase in retinal interneuron amacrine cells and Zn2+ is then transferred to RGCs via the Zn2+ transporter protein ZnT-3, triggering RGC loss in optic nerve injury. Zn2+ chelation and ZnT-3 deletion promote long-term RGC survival. However, the downstream signaling pathways of Zn2+ in RGCs remains unknown. Here, we show that increased levels of Zn2+ upregulate the expression and activity of mitochondrial zinc metallopeptidase OMA1 in the retina, leading to the cleavage of DELE1 and activation of cytosolic eIF2α kinase PKR, triggering the integrated stress response (ISR) in RGCs. Our study identified OMA1 and ISR as the downstream molecular mechanisms of retinal Zn2+ and potential targets for preventing the progression of Zn2+-associated neuronal damage.

This study aimed to analyze the quantitative vascular biomarkers of filtering bleb function at different depths using anterior segment optical coherence tomography angiography (AS-OCTA). This cross-sectional study is registered on Clinicaltrails.gov (NCT 04515017). Forty-six eyes with primary open-angle glaucoma that had undergone trabeculectomy with mitomycin-C for more than six months were included. Vessel density (VD) and vessel diameter index (VDI) in the superficial layer (SL), Tenon’s layer (TL), and deep layer (DL) of the bleb were obtained. The VD and VDI were higher in the failure group (both p = 0.000). Significant correlations were found between the SL, TL, DL’s VDI, and IOP in the success group (p = 0.013, 0.016, 0.031, respectively). The VD of the TL and DL were related to IOP in the failure group (p = 0.012, 0.009). Tenon’s VD (TVD) and Tenon’s VDI (TVDI) correlated with IOP adjusting for TVD, TVDI, and the Indiana Bleb Appearance Grading Scale (IBAGS) (p = 0.009, 0.043) or Kenfeld grading system (KGS) (p = 0.011, 0.016). The area under curve (AUC) of the TVD, TVDI, IBAGS, and KGS to predict surgery failure were 0.960, 0.925, 0.770, and 0.850. AS-OCTA realized the quantitative evaluation of vessels, especially the invisible vascularity beneath the conjunctiva. TVD and TVDI as detected by AS-OCTA better reflected bleb function than conventional grading systems.

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AimsTo evaluate the psychometric properties of a newly designed questionnaire, the 40-item Glaucoma Visual Functioning Questionnaire (GVFQ-40), in a Chinese sample to capture the visual ability of patients with glaucomatous vision impairment in five domains.MethodsEighty-four glaucoma suspects (controls) and 270 glaucoma patients were recruited from the Glaucoma Clinic at Zhongshan Ophthalmic Centre in this cross-sectional, observational study. All subjects completed two questionnaires during routine clinical visits: the GVFQ-40 and the validated National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25). The discriminant, criterion-related and construct validity of the GVFQ-40 were assessed. A subset of subjects completed the GVFQ-40 twice, with an interval of 7–21 days, to determine test–retest reliability.ResultsDomain-specific and total GVFQ-40 scores were significantly higher (worse visual ability) in glaucoma patients than in controls (all p<0.001). All pairwise subgroup comparisons were statistically significant except for the ‘mobility’ domain comparison between the mild visual field loss and control groups (p=0.189). Significant differences between these two groups were observed in only 2 of the 12 dimensions on the NEI VFQ-25. The GVFQ-40 results demonstrated strong correlations with better-eye mean deviation and Visual Field Index (glaucoma severity measures). Exploratory factor analysis tended to confirm a three-domain structure. Test–retest intraclass correlation coefficients were higher than 0.927 for domain-specific and total GVFQ-40 scores.ConclusionsThe GVFQ-40 possesses good validity and reliability. It can be used to evaluate the impact of glaucomatous damage on visual ability and has potential in the evaluation of intervention efficacy.Trial registration numberNCT04722861.