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Gene expression in the mouse retina: the effect of damaging light
1Department of Ophthalmology, University Eye Clinic, Zurich, Switzerland. cgrimm@opht.unizh.ch
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.
Insights
Intense light exposure upregulates AP-1 transcription factors, c-fos and c-jun, in the retina. This process is linked to photoreceptor apoptosis, with caspase-1 playing a potential role in light-induced retinal degeneration.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- High-intensity visible light causes photoreceptor cell death via apoptosis.
- This apoptotic process is known to involve the activation of the transcription factor AP-1.
- Investigating gene expression changes is crucial for understanding light-induced photoreceptor damage.
Purpose of the Study:
- To measure the expression of AP-1 family members and apoptosis-related genes.
- To determine the involvement of these genes in light-induced photoreceptor apoptosis.
- To elucidate the role of gene regulation in retinal degeneration.
Main Methods:
- Exposure of wildtype and c-fos knockout mice to high-intensity visible light.
- RNA extraction from retinas during and after light exposure.
- Semiquantitative analysis of mRNA levels using RT-PCR.
Main Results:
- Intense light induced c-fos and c-jun mRNA expression in wildtype mice.
- c-fos expression peaked early, while c-jun expression persisted longer.
- Caspase-1 expression was upregulated in wildtype mice but not in c-fos knockout mice, which were protected from apoptosis.
Conclusions:
- Light-induced photoreceptor apoptosis involves the transient induction of c-fos and c-jun.
- Caspase-1 upregulation by light suggests its involvement in retinal degeneration.
- The absence of c-Fos protects mice from light-induced photoreceptor cell death.