title: The rat with oxygen-induced retinopathy is myopic with low retinal dopamine.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Tara L
authors.initials: TL
authors.lastname: Favazza
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Baglieri
authors.forename: Ilan Y
authors.initials: IY
authors.lastname: Benador
authors.forename: Emily R
authors.initials: ER
authors.lastname: Noonan
authors.forename: Anne B
authors.initials: AB
authors.lastname: Fulton
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Hansen
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.forename: James D
authors.initials: JD
authors.lastname: Akula
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004596:Electroretinography; D009216:Myopia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000503:physiopathology; D055351:Retinal Neurons / Q000378:metabolism*; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D042262:Retinoscopy
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D010100:Oxygen; D004298:Dopamine
keywords: development; dopamine; myopia; ocular; rat; retinopathy of prematurity