title: RPE65 is essential for the function of cone photoreceptors in NRL-deficient mice.
abstract: OBJECTIVE
  Phototransduction in cones is initiated by the bleaching of their visual pigment, which comprises a protein component-cone opsin-and a vitamin A derivative-11-cis retinal. Little is known about the source of 11-cis retinal for cones. In the current study, neural retina leucine zipper-deficient (Nrl(-/-)) and rod opsin (Rho(-/-))-deficient mice were used, two mouse models that have been described as having a "cone-only" retina, to analyze the retinoid metabolism of cones. In addition, these mice were bred to retinal pigment epithelial protein 65 (Rpe65(-/-))-deficient mice to study the role of RPE65.
  
  
  METHODS
  Mice were analyzed using morphology, Western blot analysis, immunohistochemistry, electroretinography (ERG), and retinoid profiling by HPLC.
  
  
  RESULTS
  In comparison to wild-type mice, the retina of Nrl(-/-) mice contained elevated levels of RPE65 and cellular retinaldehyde-binding protein (CRALBP), suggesting a particular role of these two proteins for the retinoid metabolism of cones. In Nrl(-/-) mice, different retinoid species were present in proportions similar to wild type. Ablation of RPE65 in Nrl(-/-) and Rho(-/-) mice led to the absence of 11-cis retinal, but increased the total retinoid content, with retinyl esters representing the most abundant retinoid species. In the absence of RPE65, retinal sensitivity in Nrl(-/-) mice dropped by a factor of a thousand.
  
  
  CONCLUSIONS
  The data show that RPE65, previously shown to be essential for rod function, is also indispensable for the production of 11-cis retinal for cones and thus for cone function.
authors.affiliation: Laboratory for Retinal Cell Biology, Eye Clinic, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wenzel
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
authors.forename: Vitus
authors.initials: V
authors.lastname: Oberhauser
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanimoto
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency* / Q000235:genetics; D015153:Blotting, Western; D002352:Carrier Proteins / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D007150:Immunohistochemistry; D016350:Leucine Zippers / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D012172:Retinaldehyde; D017299:Rod Opsins / Q000172:deficiency / Q000235:genetics; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D005136:Eye Proteins; D012172:Retinaldehyde; D017299:Rod Opsins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C020932:11-cis-retinal-binding protein; C084884:Nrl protein, mouse