title: ATP-induced photoreceptor death in a feline model of retinal degeneration.
abstract: OBJECTIVE
  To develop and characterize a feline model of retinal degeneration induced by intravitreal injection of adenosine triphosphate (ATP).
  
  
  METHODS
  Nineteen normally sighted adult cats received 100 μL intravitreal injections of ATP with a final concentration of 11, 22, or 55 mM at the retina. Four animals were euthanized 30 hours after injection and retinal sections examined for apoptosis using a TUNEL cell death assay. In the remaining animals, structural and functional changes were characterized over a 3-month period using a combination of electroretinography (ERG) and optical coherence tomography (OCT).
  
  
  RESULTS
  Using a TUNEL cell death assay, we detected widespread photoreceptor death 30 hours after injection with 55 mM intravitreal ATP. All concentrations of ATP caused loss of retinal function and gross changes in retinal structure within 2 weeks of injection. Intravitreal injection of ATP led to a rapid loss of rod photoreceptor function and a gradual loss of cone photoreceptor function within 3 months. Outer nuclear layer thickness was globally reduced by 3 months, with the inner nuclear layer including the retinal nerve fiber layer remaining intact. Structural abnormalities were observed, including focal retinal detachment with evidence of both intravitreal and intraretinal inflammation in some eyes.
  
  
  CONCLUSIONS
  Development of an ATP-induced feline model of retinal degeneration provides a rapid and effective large-eyed animal model for research into vision restoration.
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Felix P
authors.initials: FP
authors.lastname: Aplin
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Chi D
authors.initials: CD
authors.lastname: Luu
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Kirstan A
authors.initials: KA
authors.lastname: Vessey
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.affiliation: The Bionics Institute, East Melbourne, Victoria, Australia Medical Bionics Department, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Shepherd
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Fletcher
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002415:Cats; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects; D058449:Intravitreal Injections; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects* / Q000502:physiology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects* / Q000502:physiology; D041623:Tomography, Optical Coherence
chemical_list: D000255:Adenosine Triphosphate
keywords: ATP-induced retinal degeneration; animal model; feline; photoreceptor; retinitis pigmentosa