title: Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews.
abstract: We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 µL intravitreal injections in the FD eye. The reference group received 0.85% NaCl vehicle. Four groups received a higher, or lower, dose of a D1-like receptor agonist (SKF38393) or antagonist (SCH23390). Four groups received a higher, or lower, dose of a D2-like receptor agonist (quinpirole) or antagonist (spiperone). Two groups received the D4 receptor agonist (PD168077) or antagonist (PD168568). Refractions were measured daily; axial component dimensions were measured on day 1 (before treatment) and day 12. We found that in groups receiving the D1-like receptor agonist or antagonist, the development of FDM and altered ocular component dimensions did not differ from the NaCl group. Groups receiving the D2-like receptor agonist or antagonist at the higher dose developed significantly less FDM and had shorter vitreous chambers than the NaCl group. The D4 receptor agonist, but not the antagonist, was nearly as effective as the D2-like agonist in reducing FDM. Thus, using intravitreally-administered agents, we did not find evidence supporting a role for the D1-like receptor pathway in reducing FDM in tree shrews. The reduction of FDM by the dopamine D2-like agonist supported a role for the D2-like receptor pathway in the control of FDM. The reduction of FDM by the D4 receptor agonist, but not the D4 antagonist, suggests an important role for activation of the dopamine D4 receptor in the control of axial elongation and refractive development.
authors.affiliation: Genetics, Genomics and Bioinformatics Theme,University of Alabama at Birmingham,Birmingham,AL 35294.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Ward
authors.affiliation: Department of Optometry and Vision Science,University of Alabama at Birmingham,Birmingham,AL 35294.
authors.forename: John T
authors.initials: JT
authors.lastname: Siegwart
authors.affiliation: Department of Optometry and Vision Science,University of Alabama at Birmingham,Birmingham,AL 35294.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Frost
authors.affiliation: Department of Optometry and Vision Science,University of Alabama at Birmingham,Birmingham,AL 35294.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Norton
mesh_terms: D000818:Animals; D058452:Axial Length, Eye / Q000473:pathology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D058449:Intravitreal Injections; D008297:Male; D013058:Mass Spectrometry; D009216:Myopia / Q000188:drug therapy*; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050638:Receptors, Dopamine D4 / Q000819:agonists* / Q000037:antagonists & inhibitors; D012029:Refraction, Ocular / Q000187:drug effects*; D012683:Sensory Deprivation; D014418:Tupaiidae
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4
keywords: Dopamine; Emmetropization; Form-deprivation myopia; Intravitreal injection; Refractive development