title: Light prevents exogenous 11-cis retinal from maintaining cone photoreceptors in chromophore-deficient mice.
abstract: OBJECTIVE
  To determine the effect of light/dark cycles on the cones of 11-cis retinal-treated RPE65/rhodopsin double knockout (Rpe65(-/-)Rho(-/-)) mice. Studies have shown that cones degenerate in chromophore-deficient mouse models for Leber Congenital Amaurosis (LCA), but exogenous supplementation of the native 11-cis retinal chromophore can inhibit this degeneration, suggesting that 11-cis retinal could be used as a therapeutic agent for preserving functional cones in patients with LCA. However, these treated mice were maintained in the dark.
  
  
  METHODS
  11-cis Retinal was introduced into Rpe65(-/-)Rho(-/-) mice at postnatal day 10 as a single subcutaneous injection mixed with a basement membrane matrix. The mice were maintained in either normal light/dark cycles or constant dark conditions. Fluorescence microscopy was used to assess retinal morphology. Cone cell survival was determined by counting cone opsin-containing cells on flat-mounted P30 retinas. Cross-sections of P21 mouse retina were used to assess cone cell integrity by visualizing opsin localization. Cone function was determined by electroretinography (ERG).
  
  
  RESULTS
  Previous studies have shown that 11-cis retinal-treated mice lacking RPE65 and raised in constant dark have higher cone photoreceptor cell number, improved cone opsin localization, and enhanced cone ERG signals when compared with untreated mice. However, in this study the authors show that 11-cis retinal-treated Rpe65(-/-)Rho(-/-) mice raised in cyclic light did not show the improvements seen with the dark-reared mice.
  
  
  CONCLUSIONS
  Thus, 11-cis retinal by itself, as well as other agents that form photosensitive pigments, will not be good therapeutic candidates for preserving cones in LCA.
authors.affiliation: Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.forename: Rosalie K
authors.initials: RK
authors.lastname: Crouch
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kono
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002452:Cell Count; D002470:Cell Survival; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D055786:Gene Knockout Techniques; D057130:Leber Congenital Amaurosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D055355:Opsins / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology* / Q000528:radiation effects; D012172:Retinaldehyde / Q000627:therapeutic use*; D012243:Rhodopsin / Q000235:genetics*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D055355:Opsins; D012172:Retinaldehyde; D012243:Rhodopsin; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase