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R. Kehat, E. Zemel, H. Soreq, I. Perlman; Antisense therapy directed against AChE attenuates light induced retinal damage in a rat model . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4777.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously shown (ARVO 2001) that Acetylcholinesterase (AChE) expression in the inner segments of rat photoreceptors is increased following exposure to damaging light. Since there are no cholinergic synapses in this region of the retina, we suggested that AChE played a role in the rods' response to stress. Here, we investigated the role of AChE in the recovery of photoreceptors from light–induced retinal damage. Methods:Albino rats were exposed to 20–28 hrs of bright light. Animals were treated for 30 days with daily intra–peritoneal injections of antisense, capable of preventing the accumulation of the readthrough isoform of AChE, beginning one day before light exposure (n=10). Injections of saline served as controls (n=10). Retinal function was assessed from the electroretinograms (ERGs) that were recorded 0,1,7,14 and 30 days after light exposure. At the same time intervals, rats were sacrificed and their eyes enucleated. AChE–S, –R mRNA levels and distributions were examined by in–situ hybridization, while AChE activity was assessed by cytochemical staining. Results:Following light exposure Vmax of a–, b– waves deteriorated till 7 days, then slightly recovered but remained significantly low. AChE–S, –R mRNA and AChE activity levels were low in the normal retina, but, increased after light exposure in the inner segments of the photoreceptors. AChE antisense therapy attenuated the decrease in the ERG Vmax following light damage. This was accompanied by a marked reduction of the AChE activity in the light exposed photoreceptors. Conclusions:These results suggest that the stress–induced AChE protein in rat photoreceptors has a detrimental role. AChE antisense therapy is effective in preventing the increase in expression of AChE following light exposure. This mode of therapy enhanced retinal functional recovery of light exposed rats. Further studies will determine the role of antisense therapy modality in the prevention of photoreceptor damage.
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