Light affects mitochondria to cause apoptosis to cultured cells: possible relevance to ganglion cell death in certain optic neuropathies.
Retinal ganglion cell axons within the globe are laden with mitochondria that are unprotected from light (400-760 nm) impinging onto the retina. Light can be absorbed by mitochondrial enzymes such as cytochrome and flavin oxidases causing the generation of reactive oxygen species, and we have suggested this may pose a risk to ganglion cell survival if their energy state is compromised, as may be so in glaucoma or in Leber's Hereditary Optic Neuropathy. Here, we demonstrate that light (400-760 nm) provokes apoptosis in cultured retinal ganglion-5 cells, and that this effect is enhanced in low serum, and attenuated by various antioxidants. Apoptosis is shown to be caspase independent, involving reactive oxygen species generation and the activation of poly(ADP-ribose) polymerase-1 and apoptosis-inducing factor. We further show that light-induced apoptosis requires the participation of the mitochondrial respiratory chain. This was demonstrated by culturing fibroblasts (BJhTERT cells) in ethidium bromide for 40 days to deplete their mitochondrial DNA and perturb their mitochondrial respiratory chain function (BJhTERT rh0 cells). Only BJhTERT cells, with intact mitochondrial respiratory chain function were affected by light insult. Finally, we show that exposure of anaesthetized pigmented rat eye to white, but not red light, causes changes in the expression of certain retinal mRNAs (neurofilament light, Thy-1 and melanopsin) and optic nerve proteins (neurofilament light and tubulin), suggesting that ganglion cell survival is affected. Our findings support the proposal that the interaction of light, particularly the blue component, with intra-axonal ganglion cell mitochondria may be deleterious under certain circumstances, and suggest that reducing the light energy impinging upon the retina might benefit patients with certain optic neuropathies.
Osborne
Neville N
NN
Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK. neville.osborne@eye.ox.ac.uk
Li
Guang-Yu
GY
Ji
Dan
D
Mortiboys
Heather J
HJ
Jackson
Sandra
S
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D016923:Cell Death / Q000528:radiation effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D008027:Light / Q000009:adverse effects*; D051379:Mice; D008928:Mitochondria / Q000473:pathology / Q000528:radiation effects*; D009901:Optic Nerve Diseases / Q000209:etiology / Q000473:pathology*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000528:radiation effects*