Red light provides partial protection against retinal ganglion cell degeneration in a mouse model of dominant optic atrophy through the activation of NFkB

Abstract

PurposeMutations in OPA1 are the leading cause of dominant optic atrophy, a disease in which a progressive loss of retinal ganglion cells (RGCs) leads to blindness. In the B6;C3‐Opa1Q285STOP mouse, an Opa1 mutation causes a decrease in ATP production and a progressive loss in visual acuity, which coincides with pruning of the predominantly ON‐centre RGC dendrites. Explanting the retina, initiates further dendritic pruning. Red light has been shown to increase ATP production and provide neuroprotection. We hypothesised that 670 nm light can delay ex vivo dendritic pruning in the B6;C3‐Opa1Q285STOP mouse.MethodsWe therefore monitored the effects of 670 nm light (radiant exposure of 26.4 J/cm2) on RGC dendritic pruning in retinal explants from B6;C3‐Opa1Q285STOP mice, after 16 hours ex vivo.ResultsThe area under the Sholl curves, the peak of the Sholl curves and the total dendritic length of ON‐center RGCs showed statistically significant reductions by 28% (p<0.05), 27% (p<0.05) and 29% (p<0.05), respectively, from 0 to 16 hours ex vivo, with sham treatment but no statistically significant reductions were seen with 670 nm light treatment. An increase in the nuclear‐cytoplasmic ratio of transcription factor, NfkB, but not Nrf2, was found in the ganglion cell layer with 670 nm light treatment.ConclusionsThe results demonstrate the ability of 670 nm light to partially prevent ex vivo dendropathy in the B6;C3‐Opa1Q285STOP mouse retina, and that the transcription factor NfkB, but not Nrf2, plays a role. The findings suggests that 670 nm light may also delay the RGC dendritic pruning that occurs in vivo in the B6;C3‐Opa1Q285STOP mouse and ultimately provide neuroprotection against RGC degeneration in patients with dominant optic atrophy.