title: Fundus Camera-Delivered Light-Induced Retinal Degeneration in Mice With the RPE65 Leu450Met Variant is Associated With Oxidative Stress and Apoptosis.
abstract: OBJECTIVE
  Oxidative stress, partly due to light, has an important role in many retinal diseases, including macular degeneration and retinal dystrophies. The Leu450Met variant of RPE65 is expressed in C57BL/6 and in many genetically modified mice. It confers significant resistance to light induced retinal degeneration (LIRD). Our goal was to develop an effective and efficient method to induce LIRD in resistant mice that would recapitulate mechanisms seen in known models of LIRD.
  
  
  METHODS
  The retinas of C57BL/6J mice were exposed to light using a murine fundus camera. Two protocols (with and without intraperitoneal fluorescein) were used. Optical coherence tomography (OCT) helped determine the location and extent of retinal damage. Histology, TUNEL assay, quantitative (q) PCR, and immunohistochemistry were performed.
  
  
  RESULTS
  Both protocols consistently generated LIRD in C57BL/6J mice. Optical coherence tomography and histology demonstrated that retinal damage starts at the level of the photoreceptor/outer retina and is more prominent in the superior retina. Fundus camera-delivered light-induced retinal degeneration (FCD-LIRD) is associated with apoptosis, subretinal microglia/macrophages, increased expression of oxidative stress response genes, and C3d deposition.
  
  
  CONCLUSIONS
  We characterize two new models of light-induced retinal degeneration that are effective in C57BL/6J mice, and can be modulated in terms of severity. We expect FCD-LIRD to be useful in exploring mechanisms of LIRD in resistant mice, which will be important in increasing our understanding of the retinal response to light damage and oxidative stress.
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors: Xin
authors: X
authors: Zhong
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors: Bogale
authors: B
authors: Aredo
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors: Yi
authors: Y
authors: Ding
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors: Kaiyan
authors: K
authors: Zhang
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors: Cynthia X
authors: CX
authors: Zhao
authors: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors: Rafael L
authors: RL
authors: Ufret-Vincenty
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D041623:Tomography, Optical Coherence; D019745:cis-trans-Isomerases / Q000096:biosynthesis / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
chemical_list: D012313:RNA; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase