Manjot K. Grewal

This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential.

Quantitative autofluorescence (qAF8) level is a presumed surrogate marker of lipofuscin content in the retina. We investigated the changes in the qAF8 levels in non-neovascular AMD. In this prospective cohort study, Caucasians aged ≥50 years with varying severity of non-neovascular AMD in at least one eye and Snellen visual acuity ≥6/18 were recruited. The qAF8 levels were analysed in the middle eight segments of the Delori pattern (HEYEX software, Heidelberg, Germany). The AMD categories were graded using both the Beckman classification and multimodal imaging (MMI) to include the presence of subretinal drusenoid deposits (SDD). A total of 353 eyes from 231 participants were analyzed. Compared with the age-matched controls, the qAF8 values decreased in the eyes with AMD (adjusted % difference = −19.7% [95% CI −28.8%, −10.4%]; p < 0.001) and across the AMD categories, (adjusted % differences; Early, −13.1% (−24.4%, −1%), p = 0.04; intermediate AMD (iAMD), −22.9% (−32.3%, −13.1%), p < 0.001; geographic atrophy −25.2% (−38.1%, −10.4%), p = 0.002). On MMI, the qAF8 was reduced in the AMD subgroups relative to the controls, (adjusted % differences; Early, −5.8% (−18.9%, 8.3%); p = 0.40; iAMD, −26.7% (−36.2%, −15.6%); p < 0.001; SDD, −23.7% (−33.6%, −12.2%); p < 0.001; atrophy, −26.7% (−39.3%, −11.3%), p = 0.001). The qAF8 levels declined early in AMD and were not significantly different between the severity levels of non-neovascular AMD, suggesting the early and sustained loss of function of the retinal pigment epithelium in AMD.