» Articles » PMID: 37391574

Oxidative Stress-Involved Mitophagy of Retinal Pigment Epithelium and Retinal Degenerative Diseases

Overview
Publisher Springer
Date 2023 Jun 30
PMID 37391574
Authors
Affiliations
Soon will be listed here.
Abstract

The retinal pigment epithelium (RPE) is a highly specialized and polarized epithelial cell layer that plays an important role in sustaining the structural and functional integrity of photoreceptors. However, the death of RPE is a common pathological feature in various retinal diseases, especially in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitophagy, as a programmed self-degradation of dysfunctional mitochondria, is crucial for maintaining cellular homeostasis and cell survival under stress. RPE contains a high density of mitochondria necessary for it to meet energy demands, so severe stimuli can cause mitochondrial dysfunction and the excess generation of intracellular reactive oxygen species (ROS), which can further trigger oxidative stress-involved mitophagy. In this review, we summarize the classical pathways of oxidative stress-involved mitophagy in RPE and investigate its role in the progression of retinal diseases, aiming to provide a new therapeutic strategy for treating retinal degenerative diseases. The role of mitophagy in AMD and DR. In AMD, excessive ROS production promotes mitophagy in the RPE by activating the Nrf2/p62 pathway, while in DR, ROS may suppress mitophagy by the FOXO3-PINK1/parkin signaling pathway or the TXNIP-mitochondria-lysosome-mediated mitophagy.

Citing Articles

FTO-mediated Nrf2 demethylation alleviates high glucose-induced oxidative stress and apoptosis in retinal pigment epithelial cells.

Cheng Q, Zhou L, Fan X, Ma M, Zhang C, Zha X Mol Biol Rep. 2025; 52(1):289.

PMID: 40053164 DOI: 10.1007/s11033-025-10400-x.


The potential role of amino acids in myopia: inspiration from metabolomics.

Xie Y, Zhang L, Chen S, Xie C, Tong J, Shen Y Metabolomics. 2024; 21(1):6.

PMID: 39676079 DOI: 10.1007/s11306-024-02207-x.


Methylglyoxal: A Key Factor for Diabetic Retinopathy and Its Effects on Retinal Damage.

Klochkov V, Chan C, Lin W Biomedicines. 2024; 12(11).

PMID: 39595078 PMC: 11592103. DOI: 10.3390/biomedicines12112512.


Oxidative Stress and Inflammation-Related mRNAs Are Elevated in Serum of a Finnish Wet AMD Cohort.

Liukkonen M, Helotera H, Siintamo L, Ghimire B, Mattila P, Kivinen N Invest Ophthalmol Vis Sci. 2024; 65(13):30.

PMID: 39546296 PMC: 11578155. DOI: 10.1167/iovs.65.13.30.


The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes.

Yu S, Zhu W, Yu L Open Life Sci. 2024; 19(1):20220958.

PMID: 39290494 PMC: 11406223. DOI: 10.1515/biol-2022-0958.


References
1.
Quinsay M, Lee Y, Rikka S, Sayen M, Molkentin J, Gottlieb R . Bnip3 mediates permeabilization of mitochondria and release of cytochrome c via a novel mechanism. J Mol Cell Cardiol. 2009; 48(6):1146-56. PMC: 2866782. DOI: 10.1016/j.yjmcc.2009.12.004. View

2.
Wu W, Tian W, Hu Z, Chen G, Huang L, Li W . ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep. 2014; 15(5):566-75. PMC: 4210082. DOI: 10.1002/embr.201438501. View

3.
Miller S, STEINBERG R . Active transport of ions across frog retinal pigment epithelium. Exp Eye Res. 1977; 25(3):235-48. DOI: 10.1016/0014-4835(77)90090-2. View

4.
Wang X, Yang H, Yanagisawa D, Bellier J, Morino K, Zhao S . Mitochondrial ferritin affects mitochondria by stabilizing HIF-1α in retinal pigment epithelium: implications for the pathophysiology of age-related macular degeneration. Neurobiol Aging. 2016; 47:168-179. DOI: 10.1016/j.neurobiolaging.2016.07.025. View

5.
Kim D, Lim S, Park M, Han H, Kim G, Park S . The involvement of phosphatidylinositol 3-kinase /Akt signaling in high glucose-induced downregulation of GLUT-1 expression in ARPE cells. Life Sci. 2006; 80(7):626-32. DOI: 10.1016/j.lfs.2006.10.026. View