Abstract
Abstract: :
Purpose: To investigate the effect of rhodopsin mutations on the retinal susceptibility to light and to determine potential protective effects of phenyl-N-tert-butylnitrone (PBN), a free radical trapping agent. Methods: Wild type (WT), P23H and S334ter rats were raised in dim (5-10 lux) or bright (400 lux) cyclic light (12L:12D) for 30 or 60 days. Rats from each group were killed for retinal morphometric analysis and rhodopsin measurements; others were exposed for 24 hours to 2700 lux light (LD). Dim-reared WT, P23H and S334ter rats were untreated or injected with PBN in water (Q6h) or with only water (Q6h). Dark-adapted electroretinograms (ERG) were recorded before and immediately after (D1) light exposure. Retinal morphometric analysis was done 6 days after light damage. Results: Dim-reared mutant rats had reduced ONL thickness, rhodopsin, and ERG amplitudes at 30 days and 60 days compared to WT. In WT, bright-rearing caused a significant reduction in rhodopsin content, leading to lower ERG values at 30 and 60 days of age. Bright-reared P23H rats had less rhodopsin at 30 days, followed by a significant reduction in the ONL thickness and ERG at 60 days of age. Bright-reared S334ter rats had a significant shortening of the OS at 30 days followed by a significant reduction of the rhodopsin content at 60 days but no effect on the ERG response at any age compared to the dim reared S334ter. Exposure to the continuous light induced an almost complete lost of function that could be prevented by PBN in WT and P23H. Although S334ter were less sensitive to LD, PBN did not protect significantly. Conclusion: PBN did not protect against the retinal degeneration induced by P23H or S334ter rhodopsin mutations, but did protect P23H from LD. Bright rearing increased the P23H retinal degeneration rate, but did not markedly affect the S334ter rats, which seem to have an endogenous protective mechanism against light damage.
Keywords: 562 retinal degenerations: hereditary • 321 antioxidants • 489 neuroprotection