title: Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes.
abstract: Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin-/- and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes.
  
  
  
  Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods.
  
  
  
  Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration.
  
  
  
  Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration.
authors.affiliation: Department of Medicine Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Haitao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medicine Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Medicine Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Aicha
authors.initials: A
authors.lastname: Saadane
authors.affiliation: Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Deoye
authors.initials: D
authors.lastname: Tonade
authors.affiliation: Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, United States.
authors.forename: Ivy
authors.initials: I
authors.lastname: Samuels
authors.affiliation: Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: Veenstra
authors.affiliation: Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.affiliation: Department of Medicine Case Western Reserve University, Cleveland, Ohio, United States 2Department of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, Ohio, United States 3Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, Ohio, United States 4Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, United States.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D055355:Opsins / Q000235:genetics / Q000378:metabolism*; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology*; D041623:Tomography, Optical Coherence
chemical_list: D055355:Opsins; D004247:DNA