title: Dopamine antagonists and brief vision distinguish lens-induced- and form-deprivation-induced myopia.
abstract: In eyes wearing negative lenses, the D2 dopamine antagonist spiperone was only partly effective in preventing the ameliorative effects of brief periods of vision (Nickla et al., 2010), in contrast to reports from studies using form-deprivation. The present study was done to directly compare the effects of spiperone, and the D1 antagonist SCH-23390, on the two different myopiagenic paradigms. 12-day old chickens wore monocular diffusers (form-deprivation) or -10 D lenses attached to the feathers with matching rings of Velcro. Each day for 4 days, 10 μl intravitreal injections of the dopamine D2/D4 antagonist spiperone (5 nmoles) or the D1 antagonist SCH-23390, were given under isoflurane anesthesia, and the diffusers (n = 16; n = 5, respectively) or lenses (n = 20; n = 6) were removed for 2 h immediately after. Saline injections prior to vision were done as controls (form-deprivation: n = 11; lenses: n = 10). Two other saline-injected groups wore the lenses (n = 12) or diffusers (n = 4) continuously. Axial dimensions were measured by high frequency A-scan ultrasonography at the start, and on the last day immediately prior to, and 3 h after the injection. Refractive errors were measured at the end of the experiment using a Hartinger's refractometer. In form-deprived eyes, spiperone, but not SCH-23390, prevented the ocular growth inhibition normally effected by the brief periods of vision (change in vitreous chamber depth, spiperone vs saline: 322 vs 211 μm; p = 0.01). By contrast, neither had any effect on negative lens-wearing eyes given similar unrestricted vision (210 and 234 μm respectively, vs 264 μm). The increased elongation in the spiperone-injected form-deprived eyes did not, however, result in a myopic shift, probably due to the inhibitory effect of the drug on anterior chamber growth (drug vs saline: 96 vs 160 μm; p < 0.01). Finally, spiperone inhibited the vision-induced transient choroidal thickening in form-deprived eyes, while SCH-23390 did not. These results indicate that the dopaminergic mechanisms mediating the protective effects of brief periods of unrestricted vision differ for form-deprivation versus negative lens-wear, which may imply different growth control mechanisms between the two.
authors.forename: Debora L
authors.initials: DL
authors.lastname: Nickla
authors.forename: Kristen
authors.initials: K
authors.lastname: Totonelly
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D058452:Axial Length, Eye / Q000000981:diagnostic imaging; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D002645:Chickens; D002829:Choroid / Q000187:drug effects / Q000473:pathology; D003261:Contact Lenses / Q000009:adverse effects*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005123:Eye / Q000254:growth & development*; D058449:Intravitreal Injections; D008027:Light; D009216:Myopia / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D050638:Receptors, Dopamine D4 / Q000037:antagonists & inhibitors; D012683:Sensory Deprivation; D013134:Spiperone / Q000008:administration & dosage / Q000494:pharmacology; D014463:Ultrasonography
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D050638:Receptors, Dopamine D4; D013134:Spiperone