Visual cycle modulation in neurovascular retinopathy

• Published in: Experimental eye research 2010-08, Vol.91 (2), p.153-161
• Main Authors: Akula, James D., Hansen, Ronald M., Tzekov, Radouil, Favazza, Tara L., Vyhovsky, Tanya C., Benador, Ilan Y., Mocko, Julie A., McGee, David, Kubota, Ryo, Fulton, Anne B.
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacology; Animals; Animals, Newborn; Arterioles; Blood vessels; Dark Adaptation; Deactivation; Disease Models, Animal; Electroretinograms; Electroretinography; Eye; Humans; Infant, Newborn; Injections, Intraperitoneal; Litter; metabolism; N-retinylacetamide; Neuromodulation; Oxygen - toxicity; Pediatrics; Photic Stimulation; Photoreceptors; Phototransduction; Rats; Rats, Sprague-Dawley; Retina; Retinal Neovascularization - physiopathology; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - physiology; Retinal Rod Photoreceptor Cells - drug effects; Retinal Rod Photoreceptor Cells - physiology; Retinal Vessels - pathology; retinoid; Retinopathy; Retinopathy of Prematurity - physiopathology; Rods; Vision, Ocular - drug effects; Vision, Ocular - physiology; visual cycle
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2010.04.008

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.