Pluto Bioinformatics

GSE86442: Investigating the role of retinol dehydrogenase 10 in the retina visual cycle

Bulk RNA sequencing

Rapid pigment regeneration is critical for the continuous function of cone photoreceptors in bright and rapidly-changing light conditions throughout the day. This process is made possible in part by the recently-characterized retina visual cycle, in which retinal Mller cells recycle spent all-trans retinol visual chromophore to 11-cis retinol and supply it to cones. As only cone photoreceptors, but not rods, can oxidize 11-cis retinol to the 11-cis retinal used for pigment regeneration, this reaction is believed to render the retina visual cycle cone-specific. However, despite the importance of the retina visual cycle for promoting cone pigment regeneration and enhancing cone function, the enzyme responsible for this key 11-cis retinol oxidation reaction is still unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10) is the enzyme that enables oxidation of 11-cis retinol in cones and access to the retina visual cycle. We created mice lacking RDH10 specifically in cones, Mller cells, or the whole retina. We also generated transgenic mice overexpressing RDH10 in rods. In vivo electroretinography (ERG) and transretinal recordings revealed normal cone photoresponses in all RDH10-deficient mouse lines. Notably, cone dark adaptation both in vivo and in the isolated retina was not affected, indicating that RDH10 is not required for the oxidation of 11-cis retinol and access to the retina visual cycle. The transgenic expression of RDH10 in mouse rods had no effect on their dark adaptation and did not enable 11-cis retinol-driven pigment regeneration. We conclude that RDH10 is not the dominant cone 11-cis dehydrogenase, leaving the question of its identity still open. SOURCE: Joseph,C,Corbo (jcorbo@wustl.edu) - Washington University School of Medicine