Faculty Collaboration Database

Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa. Sci Rep 2020 Nov 23;10(1):20382

Date

11/25/2020

Pubmed ID

33230161

Pubmed Central ID

PMC7684292

DOI

10.1038/s41598-020-77290-w

Scopus ID

2-s2.0-85096441946 (requires institutional sign-in at Scopus site)   36 Citations

Abstract

Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to restore the function of damaged mitochondria, increase the production of cytoprotective factors and prevent cell death. Our laboratory has shown that FR PBM improves functional and structural outcomes in animal models of retinal injury and retinal degenerative disease. The current study tested the hypothesis that a brief course of NIR (830 nm) PBM would preserve mitochondrial metabolic state and attenuate photoreceptor loss in a model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated with 830 nm light (180 s; 25 mW/cm²; 4.5 J/cm²) using a light-emitting diode array (Quantum Devices, Barneveld, WI) from postnatal day (p) 10 to p25. Sham-treated rats were restrained, but not treated with 830 nm light. Retinal metabolic state, function and morphology were assessed at p30 by measurement of mitochondrial redox (NADH/FAD) state by 3D optical cryo-imaging, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and histomorphometry. PBM preserved retinal metabolic state, retinal function, and retinal morphology in PBM-treated animals compared to the sham-treated group. PBM protected against the disruption of the oxidation state of the mitochondrial respiratory chain observed in sham-treated animals. Scotopic ERG responses over a range of flash intensities were significantly greater in PBM-treated rats compared to sham controls. SD-OCT studies and histological assessment showed that PBM preserved the structural integrity of the retina. These findings demonstrate for the first time a direct effect of NIR PBM on retinal mitochondrial redox status in a well-established model of retinal disease. They show that chronic proteotoxic stress disrupts retinal bioenergetics resulting in mitochondrial dysfunction, and retinal degeneration and that therapies normalizing mitochondrial metabolism have considerable potential for the treatment of retinal degenerative disease.

Author List

Gopalakrishnan S, Mehrvar S, Maleki S, Schmitt H, Summerfelt P, Dubis AM, Abroe B, Connor TB Jr, Carroll J, Huddleston W, Ranji M, Eells JT

Authors

Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
Thomas B. Connor MD Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
Janis Eells PhD Professor in the Biomedical Sciences department at University of Wisconsin - Milwaukee
Sandeep Gopalakrishnan MS, PhD Assistant Professor and Director, Biobehavioral Research Laboratory in the College of Nursing department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Animals
Disease Models, Animal
Electroretinography
Energy Metabolism
Flavin-Adenine Dinucleotide
Infrared Rays
Low-Level Light Therapy
Mitochondria
NAD
Oxidation-Reduction
Rats
Rats, Transgenic
Retinal Degeneration
Retinal Rod Photoreceptor Cells
Retinitis Pigmentosa
Tomography, Optical Coherence
Treatment Outcome