Reduced inspired oxygen decreases retinal superoxide radicals and promotes cone function and survival in a model of retinitis pigmentosa

Yogita Kanan; Sean F Hackett; Henry T Hsueh; Mahmood Khan; Laura M Ensign; Peter A Campochiaro

doi:10.1016/j.freeradbiomed.2023.01.021

Reduced inspired oxygen decreases retinal superoxide radicals and promotes cone function and survival in a model of retinitis pigmentosa

Free Radic Biol Med. 2023 Mar:198:118-122. doi: 10.1016/j.freeradbiomed.2023.01.021. Epub 2023 Feb 1.

Authors

Yogita Kanan¹, Sean F Hackett², Henry T Hsueh³, Mahmood Khan², Laura M Ensign⁴, Peter A Campochiaro⁵

Affiliations

¹ The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: ykanan1@jhmi.edu.
² The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 36736930
PMCID: PMC10000309
DOI: 10.1016/j.freeradbiomed.2023.01.021

Abstract

Retinitis pigmentosa (RP) is caused by many different mutations that promote the degeneration of rod photoreceptors and have no direct effect on cones. After the majority of rods have died cone photoreceptors begin to slowly degenerate. Oxidative damage contributes to cone cell death and it has been hypothesized that tissue hyperoxia due to reduced oxygen consumption from the loss of rods is what initiates oxidative stress. Herein, we demonstrate in animal models of RP that reduction of retinal hyperoxia by reducing inspired oxygen to continuous breathing of 11% O₂ reduced the generation of superoxide radicals in the retina and preserved cone structure and function. These data indicate that retinal hyperoxia is the initiating event that promotes oxidative damage, loss of cone function, and cone degeneration in the RP retina.

Keywords: Hypoxia; Oxidative stress; Retinal degeneration; Retinitis pigmentosa.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Disease Models, Animal
Hyperoxia* / metabolism
Oxygen / metabolism
Retina / metabolism
Retinal Cone Photoreceptor Cells / metabolism
Retinitis Pigmentosa* / genetics
Superoxides / metabolism

Substances

Superoxides
Oxygen

Grants and funding

R01 EY031041/EY/NEI NIH HHS/United States