title: Visual cycle modulation in neurovascular retinopathy.
abstract: Rats with oxygen-induced retinopathy (OIR) model the pediatric retinal disease retinopathy of prematurity (ROP). Recent findings in OIR rats imply a causal role for the rods in the ROP disease process, although only experimental manipulation of rod function can establish this role conclusively. Accordingly, a visual cycle modulator (VCM) - with no known direct effect on retinal vasculature - was administered to "50/10 model" OIR Sprague-Dawley rats to test the hypotheses that it would 1) alter rod function and 2) consequently alter vascular outcome. Four litters of pups (N=46) were studied. For two weeks, beginning on postnatal day (P) 7, the first and fourth litters were administered 6 mg kg(-1) N-retinylacetamide (the VCM) intraperitoneally; the second and third litters received vehicle (DMSO) alone. Following a longitudinal design, retinal function was assessed by electroretinography (ERG) and the status of the retinal vessels was monitored using computerized fundus photograph analysis. Rod photoreceptor and post-receptor response amplitudes were significantly higher in VCM-treated than in vehicle-treated rats; deactivation of phototransduction was also significantly more rapid. Notably, the arterioles of VCM-treated rats showed significantly greater recovery from OIR. Presuming that the VCM did not directly affect the retinal vessels, a causal role for the neural retina - particularly the rod photoreceptors - in OIR was confirmed. There was no evidence of negative alteration of photoreceptor function consequent to VCM treatment. This finding implicates the rods as a possible therapeutic target in neurovascular diseases such as ROP.
authors.affiliation: Department of Ophthalmology, Children's Hospital Boston, Boston, MA 02115-5724, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Akula
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Hansen
authors.forename: Radouil
authors.initials: R
authors.lastname: Tzekov
authors.forename: Tara L
authors.initials: TL
authors.lastname: Favazza
authors.forename: Tanya C
authors.initials: TC
authors.lastname: Vyhovsky
authors.forename: Ilan Y
authors.initials: IY
authors.lastname: Benador
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mocko
authors.forename: David
authors.initials: D
authors.lastname: McGee
authors.forename: Ryo
authors.initials: R
authors.lastname: Kubota
authors.forename: Anne B
authors.initials: AB
authors.lastname: Fulton
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D006801:Humans; D007231:Infant, Newborn; D007274:Injections, Intraperitoneal; D010100:Oxygen / Q000633:toxicity; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology; D012171:Retinal Vessels / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000503:physiopathology*; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology*
chemical_list: D000081:Acetamides; C551179:N-((2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenyl)acetamide; D010100:Oxygen