Year: 2019
Type: article
Abstract: ABSTRACT 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 believed to depend in part on an intraretinal visual cycle that supplies 11‐ cis ‐retinaldehyde to cone opsins. Candidate enzymes of this pathway have been reported, but their physiologic contribution to cone photoresponses remains unknown. Here, we evaluate the role of a candidate retinol isomerase of this pathway, sphingolipid δ4 desaturase 1 (Des1). Single‐cell RNA sequencing analysis revealed Des1 expression not only in Müller glia but also throughout the retina and in the retinal pigment epithelium. We assessed cone functional dependence on Müller cell‐expressed Des1 through a conditional knockout approach. Floxed Des1 mice, on a guanine nucleotide‐binding protein subunit α transducin 1 knockout ( Gnat1 −/− ) background to allow isolated recording of cone‐driven photoresponses, were bred with platelet‐derived growth factor receptor α (Pdgfrα)‐Cre mice to delete Des1 in Müller cells. Conditional knockout of Des1 expression, as shown by tissue‐selective Des1 gene recombination and reduced Des1 catalytic activity, caused no gross changes in the retinal structure and had no effect on cone sensitivity or dark adaptation but did slightly accelerate the rate of cone phototransduction termination. These results indicate that Des1 expression in Müller cells is not required for cone visual pigment regeneration in the mouse.—Kiser, P. D., Kolesnikov, A. V., Kiser, J. Z., Dong, Z., Chaurasia, B., Wang, L., Summers, S. A., Hoang, T., Blackshaw, S., Peachey, N. S., Kefalov, V. J., Palczewski, K. Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones. FASEB J. 33, 5782–5792 (2019). www.fasebj.org
Source: The FASEB Journal
Institutions: University of California, Irvine, Louis Stokes Cleveland VA Medical Center, VA Long Beach Healthcare System, Case Western Reserve University, Washington University in St. Louis, Polgenix (United States), University of Utah, Johns Hopkins University, Johns Hopkins Medicine, Cleveland Clinic
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,740
Funders: American Diabetes Association, U.S. Department of Veterans Affairs, American Heart Association, Research to Prevent Blindness, Cleveland Clinic, University of Washington, Case Western Reserve University, National Institutes of Health, National Eye Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G151565447, G1516904128, G1705275158, G196819017, G2139587701, G2165983446, G257729898, G2818349869, G2905266098, G311281104, PIGMENT DEPHOSPHORYLATION IN MAMMALIAN ROD AND CONE PHOTORECEPTORS, MECHANISMS OF ADAPTATION IN MAMMALIAN CONES, G4003851402, G4091336087, G412336820, G4132518751, Novel therapies to inhibit Diabetic Retinopathy, G4539512084, G5794508668, G6196185825, Use of systems pharmacology to prevent rod and cone photoreceptor degeneration, G7097900329, G7527360782, NEI Center Core Grant for Vision Research
OpenAlex ID: W2910836738