C Grimm1, A Wenzel, F Hafezi, C E Remé. 1. Department of Ophthalmology, University Eye Clinic, Zurich, Switzerland. cgrimm@opht.unizh.ch
Abstract
PURPOSE: High levels of visible light induce apoptotic cell death of photoreceptors, a process depending on the activation of the transcription factor AP-1. This suggests that regulation of gene expression might be important for light-induced photoreceptor cell death. We measured expression of AP-1 family members and of several apoptosis-related genes to test their potential involvement in photoreceptor apoptosis. METHODS: Wildtype and c-fos-/- mice were exposed to low (roomlight) or high levels of visible light for up to two hours. Total RNA was prepared from isolated retinas during and after light exposure. Relative mRNA levels were determined semiquantitatively using either competitive or exponential RT-PCR. RESULTS: Expression of c-fos-/- was upregulated by intense light as early as 15 min after lights on. Highest levels (6-fold induction) were detected at 2 h after lights off declining thereafter to basal levels 20 h after the end of exposure. c-jun mRNA was induced at 30 min after lights on and high expression levels (fourfold induction) persisted at least for 8 h. Similarly, expression of caspase-1 was six to 9-fold increased at 6 to 8 h after light exposure in wildtype but not in c-fos knockout mice. The latter mice are protected against light-induced photoreceptor apoptosis. Expression of other apoptosis-related genes (bcl-2, bcl-XL, bax, bad, caspase-3) was not affected by light exposure or the lack of c-Fos in knockout mice. CONCLUSIONS: Expression of c-fos and c-jun mRNA is transiently induced by exposure to damaging light. Induced expression of c-jun persists longer than expression of c-fos. Among the apoptosis-related genes, only caspase-1 expression was upregulated by light exposure and Caspase-1 might therefore be involved in light-induced retinal degeneration.
PURPOSE: High levels of visible light induce apoptotic cell death of photoreceptors, a process depending on the activation of the transcription factor AP-1. This suggests that regulation of gene expression might be important for light-induced photoreceptor cell death. We measured expression of AP-1 family members and of several apoptosis-related genes to test their potential involvement in photoreceptor apoptosis. METHODS: Wildtype and c-fos-/- mice were exposed to low (roomlight) or high levels of visible light for up to two hours. Total RNA was prepared from isolated retinas during and after light exposure. Relative mRNA levels were determined semiquantitatively using either competitive or exponential RT-PCR. RESULTS: Expression of c-fos-/- was upregulated by intense light as early as 15 min after lights on. Highest levels (6-fold induction) were detected at 2 h after lights off declining thereafter to basal levels 20 h after the end of exposure. c-jun mRNA was induced at 30 min after lights on and high expression levels (fourfold induction) persisted at least for 8 h. Similarly, expression of caspase-1 was six to 9-fold increased at 6 to 8 h after light exposure in wildtype but not in c-fos knockout mice. The latter mice are protected against light-induced photoreceptor apoptosis. Expression of other apoptosis-related genes (bcl-2, bcl-XL, bax, bad, caspase-3) was not affected by light exposure or the lack of c-Fos in knockout mice. CONCLUSIONS: Expression of c-fos and c-jun mRNA is transiently induced by exposure to damaging light. Induced expression of c-jun persists longer than expression of c-fos. Among the apoptosis-related genes, only caspase-1 expression was upregulated by light exposure and Caspase-1 might therefore be involved in light-induced retinal degeneration.