Refraction in an Oxygen-Induced Retinopathy (OIR) Rat Model of Retinopathy of Prematurity (ROP): Is the "ROP Rat" a Good Model?

Abstract

Purpose: : In the majority of infants with ROP, the vascular disease is mild and resolves spontaneously. Among the most common ROP sequelae is refractive error. Paradoxically, ROP and premature birth are associated both with increased magnitude and prevalence of myopia and also with shorter axial length. Higher refractive power of the anterior segment (e.g., steeper cornea, increased lens thickness) may underpin the myopia. Molecular controllers of refractive development, including dopamine (DA), are found in the neural retina. The OIR rat has shorter axial length (Akula et al., 2009); whether it is also myopic was investigated.

Methods: : The Penn et al. (1995) "50/10" OIR model (ROP rats, n=9) and room-air-reared controls (RAR rats, n=10) were studied. At postnatal day (P) 27-28, cycloplegic refractions (D) were measured using an automated infrared photoretinoscope. Three rats from each group were selected for follow-up electroretinographic (ERG) analysis of retinal function at P31; ERG data from one RAR rat was lost due to a system malfunction. The amplitude (µV) of the rod (Rm_P3) and bipolar cell (Rm_P2) circulating currents were derived, as was the energy (∝J) in the OPs (Em) and retinal sensitivity (µV·cd^-1·s^-1·m²) at threshold (Sm). The remaining rats were sacrificed and the content of retinal DA and its primary metabolite (DOPAC) assessed (pg/µl) by high-pressure liquid chromatography (HPLC). A single datum (mean of all observations) was calculated for each parameter in each subject and used in the final analysis.

Results: : The ROP rats were significantly more myopic than the RAR rats (>1.8 D mean difference; t=4.1; df=17; P=0.001). Reductions in DA (t=7.8; df=10; P<0.0001) and DOPAC (t=6.7; df=10; P<0.0001) were found in ROP rats’ retinae. The ERG parameters Rm_P2 (r=0.89), Em (r=0.97), and Sm (r=0.94), as well as DA content (r=0.62), were significantly associated with refraction.

Conclusions: : Damage to the neural retina, and corresponding decreases in retinal DA content, may mediate one of the most common sequelae of ROP, refractive error. The 50/10 ROP rat well approximates the refractive status commonly found in prematurely born humans.

Keywords: refractive error development • dopamine • retinopathy of prematurity