Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

PGC-1α Regulates the Interplay between Oxidative Stress, Senescence and Autophagy in the Aging Retina Important in Age-Related Macular Degeneration

Version 1 : Received: 17 July 2023 / Approved: 17 July 2023 / Online: 18 July 2023 (11:09:42 CEST)

How to cite: Gurubaran, I. S.; Watala, C.; Kostanek, J.; Szczepanska, J.; Pawlowska, E.; Kaarniranta, K.; Blasiak, J. PGC-1α Regulates the Interplay between Oxidative Stress, Senescence and Autophagy in the Aging Retina Important in Age-Related Macular Degeneration. Preprints 2023, 2023071220. https://doi.org/10.20944/preprints202307.1220.v1 Gurubaran, I. S.; Watala, C.; Kostanek, J.; Szczepanska, J.; Pawlowska, E.; Kaarniranta, K.; Blasiak, J. PGC-1α Regulates the Interplay between Oxidative Stress, Senescence and Autophagy in the Aging Retina Important in Age-Related Macular Degeneration. Preprints 2023, 2023071220. https://doi.org/10.20944/preprints202307.1220.v1

Abstract

We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1a protein and nuclear factor erythroid 2 like 2 (NFE2L2) gene, showed some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvement of PGC-1a in AMD pathogenesis we used young (3-month) and old (12-month) mice with knockout in the PPARGC1A gene and age-matched wild-type (WT) animals. An immunohistochemical analysis showed age-dependent different expression of markers of oxidative stress defense, senescence and autophagy in the retinal pigment epithelium of KO animals as compared with their WT counterparts. Multivariate inference testing showed that senescence and autophagy proteins had the greatest impact on the discrimination between KO and WT 3-month animals, but proteins of antioxidant defense also contributed to that discrimination. A bioinformatic analysis showed that PGC-1a might coordinate the interplay between genes encoding proteins involved in antioxidant defense, senescence and autophagy in the aging retina. These data support importance of PGC-1a in AMD pathogenesis and confirm the utility of mice with PGC-1a knockout as an animal model to study AMD pathogenesis.

Keywords

age-related macular degeneration; aging retina; peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PGC-1 AMD; cellular senescence; autophagy; oxidative stress

Subject

Biology and Life Sciences, Life Sciences

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