title: The Consequences of Hypomorphic RPE65 for Rod and Cone Photoreceptors.
abstract: RPE65 is essential for both rod- and cone-mediated vision. So far, more than 120 disease-associated mutations have been identified in the human RPE65 gene. Differential clinical manifestations suggested that some patients suffer from null mutations while others retain residual RPE65 activity and some useful vision. To understand the mechanism of retinal degeneration or dysfunction caused by such hypomorphic RPE65 alleles, we generated an Rpe65 (R91W) knock-in mouse (R91W) that expresses a mutant RPE65 protein with reduced function. Data obtained suggested that the R91W mouse is highly suitable to study the impact of RPE65 insufficiency on rod pathophysiology. To study the impact on cones, we combined the R91W with the Nrl (-/-) mouse that develops an all-cone retina. Here we summarize the consequences of hypomorphic RPE65 function (reduced 11-cis-retinal synthesis) for rod and cone pathophysiology.
authors.affiliation: Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Wagistr. 14, 8952, Schlieren, Switzerland. marijana.samardzija@usz.uzh.ch.
authors.forename: Marijana
authors.initials: M
authors.lastname: Samardzija
authors.affiliation: Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Wagistr. 14, 8952, Schlieren, Switzerland. maya.barben@uzh.ch.
authors.forename: Maya
authors.initials: M
authors.lastname: Barben
authors.affiliation: Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Wagistr. 14, 8952, Schlieren, Switzerland. philipp.geiger@bluewin.ch.
authors.forename: Philipp
authors.initials: P
authors.lastname: Geiger
authors.affiliation: Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Wagistr. 14, 8952, Schlieren, Switzerland. cgrimm@opht.uzh.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D006801:Humans; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020125:Mutation, Missense; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D019745:cis-trans-Isomerases / Q000235:genetics* / Q000378:metabolism; D000099178:Retinoid Isomerohydrolase
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D005136:Eye Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C084884:Nrl protein, mouse
keywords: Blindness; Cones; Degeneration; Dystrophy; Mouse model; Nrl; Photoreceptors; R91W; RPE65; Retina