Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones

Abstract

Purpose : Cone photoreceptors are essential for vision under moderate to high illuminance and allow color discrimination. Their fast dark adaptation rate and resistance to saturation are thought to depend in part on an intraretinal visual cycle involving Müller glia that supplies 11-cis-retinaldehyde to cone opsins. Candidate enzymes of this pathway have been reported but their physiological contribution to cone photoresponses remains unknown. Here, we evaluate the role of a candidate retinol isomerase of this pathway, sphingolipid δ(4) desaturase 1 (Des1).

Methods : Des1 expression in the mouse retina was evaluated by single cell RNAseq. Cone functional dependence on Müller cell-expressed Des1 was assessed through a conditional knockout approach. Floxed Des1 mice, on a Gnat1^-/- background to allow isolated recording of cone-driven photoresponses, were bred to Pdgfrα-Cre mice to delete Des1 in Müller cells. Retinal structure was evaluated by optical coherence tomography. Retinal function was assessed by in vivo and ex vivo electroretinography.

Results : Des1 was expressed not only in Müller glia but also in most other retinal cell types. Conditional knockout of Des1 expression, as demonstrated by tissue-selective Des1 gene recombination and reduced Des1 catalytic activity, caused no gross changes in retinal structure, had no effect on cone sensitivity or dark adaptation, but did slightly accelerate the rate of cone phototransduction termination.

Conclusions : These results indicate that Des1 is not required for cone visual pigment regeneration in the mouse.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.