title: Differential effects of rapamycin on rods and cones during light-induced stress in albino mice.
abstract: OBJECTIVE
  Autophagy is a lysosomal machinery-dependent process that catabolizes cellular components/organelles and proteins in an autophagic vacuole (AV)-dependent and -independent manner, respectively. Short-term exposure of the retina to bright light results in shortening of the outer segments, concomitant with AV formation. Autophagy is also induced by continuous long-term light damage, leading to photoreceptor cell death. Here the authors examined two questions: is autophagy induced during light damage proapoptotic or antiapoptotic, and are rods and cones affected differently? To this end, Balb/c mice exposed to light damage were treated with rapamycin to increase autophagy.
  
  
  METHODS
  Balb/c and GFP-LC3 mice were treated with rapamycin/vehicle. Photoreceptor degeneration was induced by 10-day light damage. Autophagy was documented by histologic, biochemical, and molecular tools; rod and cone survival was assessed by histology and electroretinography.
  
  
  RESULTS
  Light damage resulted in rod, but not cone, cell loss. Autophagy and AV formation was elicited in response to light damage, which was amplified by rapamycin. Rapamycin treatment significantly improved rod survival and function, reduced apoptosis, and normalized cytokine production that was increased in light damage. However, AV formation in GFP-LC3 mice revealed that light damage or rapamycin treatment induced AVs in cones, concomitant with reduced cone-mediated electroretinograms.
  
  
  CONCLUSIONS
  Systemic rapamycin treatment provided rod protection; however, AV formation was induced only in cones. Thus, rapamycin may act differentially in stressed photoreceptors; rapamycin might protect rods by normalizing cytokine production, removing damaged proteins by AV-independent autophagy, or both, whereas cones might be protected by AV-dependent autophagy, possibly involving reduced photon capture.
authors.affiliation: Department of Neurosciences, Division of Research, Medical University of South Carolina, Charleston, USA.
authors.forename: Kannan
authors.initials: K
authors.lastname: Kunchithapautham
authors.forename: Beth
authors.initials: B
authors.lastname: Coughlin
authors.forename: John J
authors.initials: JJ
authors.lastname: Lemasters
authors.forename: Bärbel
authors.initials: B
authors.lastname: Rohrer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004596:Electroretinography; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008027:Light / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects*; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020123:Sirolimus