Delayed Dark Adaptation in 11–cis–retinol Dehydrogenase Deficient Mice: A Role of RDH11 in Visual Processes in vivo

Abstract

Abstract: : Purpose: Vertebrate vision is dependent upon oxidative and reductive states of retinoids within the retina. 11–cis–retinol dehydrogenase (RDH) is the final step to produce visual pigment 11–cis–retinal, and disruption of 11–cis–RDH causes fundus albipunctatus and cone dystrophy. In this pathway RDH5 is responsible for a majority of the 11–cis–RDH activity, however, RDH11 is also highly expressed in retinal pigment epitherium (RPE) cells and has dual substrate specificity for both cis and trans retinoids with NADPH specificity. To investigate the role of RDH11 in the retinoid cycle in vivo, we generated rdh11^–/– and rdh5^–/–rdh11^–/– double knockout mice. Methods: Rdh11^–/– and rdh5^–/–rdh11^–/– double knockout mice were generated, and examined with the electrophysiological and biochemical methods under illuminated condition with various intensity light stimuli as well as its role in dark condition. Results: Retinoid profiles of dark–adapted rdh11^–/– mice did not show significant differences compared with WT mice, whereas an accumulation of cis–esters was detected in rdh5^–/– and rdh5^–/–rdh11^–/– mice. Following light stimulation, 73% more cis–retinyl esters were stored in rdh5^–/–rdh11^–/– mice compared with rdh5^–/– mice. Single–flash ERG of rdh11^–/– showed normal responses under dark– and light–adapted conditions, but exhibited delayed dark adaptation following high bleaching levels. Rdh5^–/–rdh11^–/– mice also had normal ERG responses in dark– and light–adapted conditions, but had a further delay in dark adaptation relative to either rdh11^–/– or rdh5^–/– mice. Delayed dark adaptation corresponded to the rate of 11–cis–retinal regeneration in the eye. Conclusions: Rdh11^–/– mice did not show significant phenotye, but rdh5^–/–rdh11^–/– mice indicated that deficiency of rdh11 gene enphasized phenotype of rdh5^–/– mice. RDH11 plays complementary role of RDH5 in regenerataion of 11–cis–retinal in vivo. Acknowledgement: We would like to thank Drs. Carola Driessen and Jacques J. M. Janssen for rdh5^–/– mice.

Keywords: vitamin A deficiency • electroretinography: non-clinical • retinal pigment epithelium