Red light irradiation in vivo upregulates dj‐1 in the retinal ganglion cell layer and protects against axotomy‐related dendritic pruning

Abstract

Retinal ganglion cells (RGCs) undergo dendritic pruning in a variety of neurodegenera-tive diseases, including glaucoma and autosomal dominant optic atrophy (ADOA). Axotomising RGCs by severing the optic nerve generates an acute model of RGC dendropathy, which can be utilized to assess the therapeutic potential of treatments for RGC degeneration. Photobiomodulation (PBM) with red light provided neuroprotection to RGCs when administered ex vivo to wild‐type retinal explants. In the current study, we used aged (13–15‐month‐old) wild‐type and heterozygous B6;C3‐Opa1Q285STOP (Opa1+/−) mice, a model of ADOA exhibiting RGC dendropathy. These mice were pre‐treated with 4 J/cm2 of 670 nm light for five consecutive days before the eyes were enucleated and the retinas flat‐mounted into explant cultures for 0‐, 8‐ or 16‐h ex vivo. RGCs were imaged by confocal microscopy, and their dendritic architecture was quantified by Sholl analysis. In vivo 670 nm light pretreatment inhibited the RGC dendropathy observed in untreated wild‐type retinas over 16 h ex vivo and inhibited dendropathy in ON‐center RGCs in wild‐type but not Opa1+/− retinas. Immunohistochemistry revealed that aged Opa1+/− RGCs exhibited increased nitrosative damage alongside significantly lower activation of NF‐κB and upregulation of DJ‐1. PBM restored NF‐κB activation in Opa1+/− RGCs and enhanced DJ‐1 expression in both genotypes, indicating a potential molecular mechanism priming the retina to resist future oxidative insult. These data support the potential of PBM as a treatment for diseases involving RGC degeneration.