Mitophagy in the retina: Viewing mitochondrial homeostasis through a new lens

• Published in: Progress in retinal and eye research Vol. 96; p. 101205
• Main Authors: Jiménez-Loygorri, Juan Ignacio, Benítez-Fernández, Rocío, Viedma-Poyatos, Álvaro, Zapata-Muñoz, Juan, Villarejo-Zori, Beatriz, Gómez-Sintes, Raquel, Boya, Patricia
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2023
• Subjects: Age-related macular degeneration; Autophagy; Diabetic retinopathy; Glaucoma; Metabolism; Mitochondria; Mitophagy; Retinal development; Retinal homeostasis; Retinitis pigmentosa; Glaucoma; Diabetic retinopathy; Mitochondria; Retinitis pigmentosa; Age-related macular degeneration; Retinal homeostasis; Retinal development; Mitophagy; Metabolism; Autophagy
• ISSN: 1350-9462; 1873-1635; 1873-1635
• DOI: 10.1016/j.preteyeres.2023.101205

Mitochondrial function is key to support metabolism and homeostasis in the retina, an organ that has one of the highest metabolic rates body-wide and is constantly exposed to photooxidative damage and external stressors. Mitophagy is the selective autophagic degradation of mitochondria within lysosomes, and can be triggered by distinct stimuli such as mitochondrial damage or hypoxia. Here, we review the importance of mitophagy in retinal physiology and pathology. In the developing retina, mitophagy is essential for metabolic reprogramming and differentiation of retina ganglion cells (RGCs). In basal conditions, mitophagy acts as a quality control mechanism, maintaining a healthy mitochondrial pool to meet cellular demands. We summarize the different autophagy- and mitophagy-deficient mouse models described in the literature, and discuss the potential role of mitophagy dysregulation in retinal diseases such as glaucoma, diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration. Finally, we provide an overview of methods used to monitor mitophagy in vitro, ex vivo, and in vivo. This review highlights the important role of mitophagy in sustaining visual function, and its potential as a putative therapeutic target for retinal and other diseases. •Mitophagy sustains retinal homeostasis by removing damaged or superfluous mitochondria.•New tools have been recently developed to assess mitophagy in the retina in vitro, ex vivo, and in vivo.•Retinal development requires mitophagy to reprogram the metabolism of differentiating cells.•Mitophagy is altered in distinct retinal diseases, including glaucoma, diabetic retinopathy, retinal dystrophies and AMD.