The Rat With Oxygen-Induced Retinopathy Is Myopic With Low Retinal Dopamine

• Type of Material: Article
• Authors: Nan Zhang, Boston Children's Hospital; Tara L. Favazza, Boston Children's Hospital; Anna Maria Baglieri, Boston Children's Hospital; Ilan Y. Benador, Boston Children's Hospital; Emily R. Noonan, Boston Children's Hospital; Anne B. Fulton, Boston Children's Hospital; Ronald M. Hansen, Boston Children's Hospital; P Michael Iuvone, Emory University; James D. Akula, Boston Children's Hospital
• Language: English
• Date: 2013-12-01
• Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC
• Publication Version: Final Published Version
• Copyright Statement: 2013 The Association for Research in Vision and Ophthalmology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1167/iovs.13-12544
• Title of Journal or Parent Work: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
• Volume: 54
• Issue: 13
• Start Page: 8275
• End Page: 8284
• Grant/Funding Information: Supported by National Institutes of Health (NIH) Grants RC1EY020308 (JDA), R01EY004864 and P30EY006360 (PMI), Research to Prevent Blindness, Inc. (PMI), and the Massachusetts Lions Eye Research Fund (RMH).
• Keywords: AMACRINE CELL; EYE SIZE; Life Sciences & Biomedicine; FORM-DEPRIVATION MYOPIA; INTERPLEXIFORM CELLS; REFRACTIVE ERROR DEVELOPMENT; Ophthalmology; ENDOGENOUS DOPAMINE; myopia; CIRCADIAN-RHYTHMS; development; retinopathy of prematurity; ocular; rat; OCULAR GROWTH; OSCILLATORY POTENTIALS; MAMMALIAN RETINA; dopamine; Science & Technology
• Research Categories: Health Sciences, Opthamology

Abstract

PURPOSE: Dopamine (DA) is a neurotransmitter implicated both in modulating neural retinal signals and in eye growth. Therefore, it may participate in the pathogenesis of the most common clinical sequelae of retinopathy of prematurity (ROP), visual dysfunction and myopia. Paradoxically, in ROP myopia the eye is usually small. The eye of the rat with oxygen-induced retinopathy (OIR) is characterized by retinal dysfunction and short axial length. There have been several investigations of the early maturation of DA in rat retina, but little at older ages, and not in the OIR rat. Therefore, DA, retinal function, and refractive state were investigated in the OIR rat.METHODS: In one set of rats, the development of dopaminergic (DAergic) networks was evaluated in retinal cross-sections from rats aged 14 to 120 days using antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in the biosynthesis of DA). In another set of rats, retinoscopy was used to evaluate spherical equivalent (SE), electoretinography (ERG) was used to evaluate retinal function, and high-pressure liquid chromatography (HPLC) was used to evaluate retinal contents of DA, its precursor levodopamine (DOPA), and its primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC).RESULTS: The normally rapid postnatal ramification of DAergic neurons was disrupted in OIR rats. Retinoscopy revealed that OIR rats were relatively myopic. In the same eyes, ERG confirmed retinal dysfunction in OIR. HPLC of those eyes' retinae confirmed low DA. Regression analysis indicated that DA metabolism (evaluated by the ratio of DOPAC to DA) was an important additional predictor of myopia beyond OIR.CONCLUSIONS: The OIR rat is the first known animal model of myopia in which the eye is smaller than normal. Dopamine may modulate, or fail to modulate, neural activity in the OIR eye, and thus contribute to this peculiar myopia.