Support for the idea that light is a risk factor in optic neuropathies, like glaucoma

Abstract Purpose: Retinal ganglion cell (RGC) axons in the globe contain many mitochondria and it has been hypothesised that light can interact with these organelles to affect RGC survival in glaucoma. Studies on different cell‐types were conducted to support such a proposition. Methods: Near confluent cultures of RGC‐5 cells, primary rat retinal cultures, fibroblasts with normal (BJhTERT) or mitochondria depleted of mtDNA (rho0) were transferred to incubators containing light (400‐760nm; 800‐2000 lux; generally 2 days). Some of the cultures were covered with white paper to exclude the light. The cultures were then analysed for cell viability, generation of free radicals (ROS) and for death by apoptosis. Results: Oxidative status and mitochondrial dehydrogenase activity in retinal cultures (‐40±5%), RGC‐5 cells (‐20±4%) and BJhTERT cells (‐13±3%) was reduced significantly by light. Light reduced the number of GABA‐positive neurones (‐42±6%) in retinal cultures. Light caused a 3‐5 fold increase in TUNEL‐positive cells in primary retinal, RGC‐5 and BJhTERT cultures, than in the dark. ROS staining was also clearly elevated by light. The light‐induced toxic effect on the different cell types was significantly blunted by antioxidants like vitamin E and lipoic acid. Moreover, light‐induced apoptosis was caspase independent but PARP dependent. In contrast, rho0 cells that lacked functional mitochondria were unaffected by light. Conclusions: The present study shows that light can directly affect mitochondrial function to induce apoptosis. This supports the view that light can interact with the many RGC axon mitochondria to affect the viability of GCs and that this may be of significance in the progression of glaucoma.