Journal Article

Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa

Schmitt, Heather, Dubis, Adam M., Abroe, Betsy, Maleki, Sepideh, Carroll, Joseph, Huddleston, Wendy, Ranji, Mahsa, Gopalakrishnan, Sandeep, Mehrvar, Shima, Connor, Thomas B., Summerfelt, Phyllis, Eells, Janis T.

2020

Overview

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/cm 2 ; 4.5 J/cm 2 ) 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/378 / 631/61 / 692/4017 / 692/420 / 692/699 / Animal models / Animals / Bioenergetics / Cell death / Disease Models, Animal / Electron transport / Electroretinograms / Electroretinography / Energy Metabolism - radiation effects / Flavin-Adenine Dinucleotide - metabolism / Histomorphometry / Humanities and Social Sciences / Infrared Rays / Light therapy / Low-Level Light Therapy - methods / Metabolism / Mitochondria / Mitochondria - metabolism / Mitochondria - radiation effects / Morphology / multidisciplinary / NAD - metabolism / NADH / Oxidation / Oxidation-Reduction / Rats / Rats, Transgenic / Recovery of function / Redox properties / Retina / Retinal degeneration / Retinal Degeneration - diagnostic imaging / Retinal Degeneration - metabolism / Retinal Degeneration - pathology / Retinal Degeneration - radiotherapy / Retinal Rod Photoreceptor Cells - metabolism / Retinal Rod Photoreceptor Cells - pathology / Retinal Rod Photoreceptor Cells - radiation effects / Retinitis / Retinitis pigmentosa / Retinitis Pigmentosa - diagnostic imaging / Retinitis Pigmentosa - metabolism / Retinitis Pigmentosa - pathology / Retinitis Pigmentosa - radiotherapy / Rodents / Science / Science (multidisciplinary) / Structure-function relationships / Tomography, Optical Coherence / Treatment Outcome