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Review
. 2023 Jul 30;12(15):1969.
doi: 10.3390/cells12151969.

The Role of Mitophagy in Glaucomatous Neurodegeneration

Dimitrios Stavropoulos  1   2 , Manjot K Grewal  3   4 , Bledi Petriti  3   5 , Kai-Yin Chau  5 , Christopher J Hammond  6   7 , David F Garway-Heath  3 , Gerassimos Lascaratos  1   6
Affiliations
Review

The Role of Mitophagy in Glaucomatous Neurodegeneration

Dimitrios Stavropoulos et al. Cells. .

Abstract

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.

Keywords: genetics; glaucoma; glaucomatous neurodegeneration; mitochondria; mitochondrial dysfunction; mitophagy; primary open-angle glaucoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Summary of mitochondrial quality control process and mitophagy pathways. Mitochondrial dynamics comprise constant cycles of fusion and fission. When a mitochondrion is depolarized or dysfunctional, it is subjected to elimination. Impaired mitochondria are removed from a cell through two main mitophagy pathways, the PTEN-induced kinase 1 (PINK1)/ Parkin RBR E3 ubiquitin protein ligase (PARKIN) pathway, which is a ubiquitin-mediated pathway, and the receptor-mediated pathway. At the beginning of the PINK1/PARKIN pathway, PINK1 is stabilized in the outer mitochondrial membrane (OMM) and recruits PARKIN, which is an E3 ubiquitin ligase. Consequently, PARKIN polyubiquitinates various OMM proteins. In turn, the polyubiquitin chains are identified by adaptor proteins such as optineurin (OPTN), which interact with microtubule-associated protein 1A/1B-light chain 3 (LC3), and as a result, the impaired mitochondrion gets isolated via a phagophore in the double-membraned autophagosome. During the receptor-mediated pathway, mitophagy receptors, such as BCL2-interacting protein 3 (BNIP3)/NIX or autophagy and beclin 1 regulator 1 (AMBRA1), attach to the interaction region of LC3, allowing them to interact directly with the phagophore. In the aftermath, the impaired mitochondrion will end up in the autophagosome where, after fusion with lysosomes, it will get degraded.
Figure 2
Figure 2
Synopsis of the main effects that proteins derived from mitophagy-related genes have on mitophagy and mitophagy pathways.
See this image and copyright information in PMC

References

    1. GBD 2019 Blindness and Vision Impairment Collaborators. Vision Loss Expert Group of the Global Burden of Disease Study Causes of Blindness and Vision Impairment in 2020 and Trends over 30 Years, and Prevalence of Avoidable Blindness in Relation to VISION 2020: The Right to Sight: An Analysis for the Global Burden of Disease Study. Lancet Glob. Health. 2021;9:e144–e160. doi: 10.1016/S2214-109X(20)30489-7. - DOI - PMC - PubMed
    1. Quartilho A., Simkiss P., Zekite A., Xing W., Wormald R., Bunce C. Leading Causes of Certifiable Visual Loss in England and Wales during the Year Ending 31 March 2013. Eye. 2016;30:602–607. doi: 10.1038/eye.2015.288. - DOI - PMC - PubMed
    1. Kang J.M., Tanna A.P. Glaucoma. Med. Clin. N. Am. 2021;105:493–510. doi: 10.1016/j.mcna.2021.01.004. - DOI - PubMed
    1. Quigley H.A., Dunkelberger G.R., Green W.R. Chronic Human Glaucoma Causing Selectively Greater Loss of Large Optic Nerve Fibers. Ophthalmology. 1988;95:357–363. doi: 10.1016/S0161-6420(88)33176-3. - DOI - PubMed
    1. Ju W.-K., Perkins G.A., Kim K.-Y., Bastola T., Choi W.-Y., Choi S.-H. Glaucomatous Optic Neuropathy: Mitochondrial Dynamics, Dysfunction and Protection in Retinal Ganglion Cells. Prog. Retin. Eye Res. 2022;95:101136. doi: 10.1016/j.preteyeres.2022.101136. - DOI - PubMed