Evaluation of the Role of Ogg1 in Mouse Retina

Abstract

Purpose: : Because of its high consumption of oxygen and its exposition to light, the retina is strongly susceptible to oxidative stress. 8–oxoguanine (8–oxoG), which is the main DNA base lesion generated by oxygen free radicals, is excised by 8–oxoguanine glycosylase (OGG1) through base excision repair (BER). A recent study reported that this enzyme might protect photoreceptor synaptic mitochondrial DNA in a model of light–induced injury. The purpose of the present study was to evaluate the effect of basal lighting conditions on the retina of wild type and OGG1^–/– mice

Methods: : C57bl6 mice were acclimated to 12h light/12 h dark photocycle (group 1), dark–adapted for 24h (group 2) or dark–adapted for 24h then exposed to light for 6h (group 3). OGG1 and BER enzymes gene expression in the neuroretina was examined by RT–PCR and the ocular localizations of the corresponding proteins were analyzed by immunohistochemistry. OGG1 activity was measured by DNA glycosylase assay. Retinal phenotype of OGG1^–/– mice was determined by electroretinographical and histological analyzes.

Results: : OGG1 protein was expressed in lens, corneal epithelium, inner segments of photoreceptors, inner nuclear layer and ganglion cell layer. No modification of protein localization and messenger expression of BER elements was observed between the different groups. In 21 day–old OGG1^–/– mice, b–wave rod amplitude was significantly reduced in comparison to control animals whereas retinal function was comparable among KO and control mice at 16 months of age. Morphologic analyzes showed that retinal structure was consistently modified in OGG1^–/– mice .

Conclusions: : This study demonstrates that mice retinal cells express OGG1 and the main elements of the BER. We suggest that, in basal condition of oxygen free radicals generation, OGG1 is not or poorly activated. Nevertheless, according to our preliminary results, OGG1 seems to be important is the maintenance of morphologic and functional retinal integrity.

Keywords: protective mechanisms • antioxidants • electroretinography: non-clinical