The Retina and Refractive Outcome in the Rat Model of ROP

Abstract

Purpose: : To determine whether retinal dysfunction and dopaminergic (DAergic) signaling in the Penn et al. (1994) oxygen-induced retinopathy "ROP rat" model are associated with altered refractive outcome.

Methods: : Cycloplegic retinoscopy was performed in adult ROP and room-air-reared (RAR) rats to measure the spherical equivalent (Rx, diopters) of their eyes. Electroretinograms (ERGs) were then recorded and parameters describing the amplitude and sensitivity of responses in the rod photoreceptors (Rm_P3, S) and postreceptor neurons (Rm_P2, K_P2) derived. Following ERG, half of the ROP and RAR rats were injected with the DOPA decarboxylase inhibitor NSD1015. One retina from each animal was studied immunohistochemically with tyrosine hydroxylase (TH) antisera. The other retina was evaluated by HPLC for dopamine (DA), its precursor DOPA, and its metabolite DOPAC. The ratio of DA to DOPAC was calculated. Following log transform of all data other than Rx, ANOVA was employed. Multiple linear regression with target Rx and predictors Rm_P3, S, Rm_P2, DOPA, and DA/DOPAC ratio was then employed to determine features associated with refractive outcome.

Results: : ROP rats were significantly more myopic than RAR rats (≥1.6 D). DA and DOPAC (but not DOPA) levels were significantly lower (>0.2 log unit) in ROP than RAR retinae. NSD1015 caused significant accumulation of DOPA (>1 log unit) and depletion of DA (>0.2 log unit) in both ROP and RAR retinae, but caused no significant change in DOPAC level. The number of TH+ processes of DAergic amacrine cells in IPL and OPL was markedly reduced in ROP (>0.7 log unit). Regression revealed that ROP, Rm_P3, Rm_P2, DA/DOPAC and S were all significant, independent predictors of refractive outcome (in diminishing importance). Combined, the respective rod response parameters (0.21+0.17=0.39) were even more predictive of Rx than ROP (0.24).

Conclusions: : The ROP rat is relatively myopic. Rod dysfunction is associated with altered refractive outcomes. DA activity, which may mediate signal transduction in the retina, is also associated with refractive outcome. The low DA in ROP retinae is likely a consequence of impaired enzymatic conversion from DOPA.

Keywords: oxidation/oxidative or free radical damage • myopia • dopamine