Abstract
Purpose::
Retinopathy of prematurity (ROP) is usually characterized by abnormal retinal vasculature. Though the involvement of rod photoreceptors and post-receptor neurons in the pathogenesis of ROP is documented in ROP subjects (both animal models and infant and child ROP patients), a causal relationship of neural and vascular outcomes has not been established. Following a longitudinal design, we assessed both the neural retina and its vasculature in rat models of ROP.
Methods::
Two rat ROP models were studied and compared to room-air reared controls. The first model was induced by exposing newborn rats (n=12)to alternating 50/10% oxygen from postnatal day (P) 0-14, the second by exposing rats (n=12)to 75% oxygen from P7-14. In the same sessions, digital fundus images and electroretinogram (ERG) records were obtained at P20±1, P30±1, and P60±1. Blood vessel integrated curvature (IC) was calculated using Retinal Image multiScale Analysis (RISA) software; IC is reminiscent of increased tortuosity of Plus disease in ROP infants. Rod photoreceptor and post-receptor function were derived from the ERG a- and b-waves. Significant changes in each RISA and ERG parameter were detected by two-factor (group; age) repeated measures analysis of variance. Linear regression was used to determine correlations between RISA and ERG parameters.
Results::
In both models, IC was initially high. In the 50/10% model IC decreased nearly to normal by 60 days, but in the 75% model IC remained high. Tortuosity in arterioles (ICA) was significantly higher than in venules (ICV). At P20, rod sensitivity (SRod) was significantly correlated with ICA and ICV. Furthermore, SRod at P20 predicted ICA at P30 and P60. On the other hand, the blood vessel parameter ICA at P20 did not predict functional outcome for receptor or post-receptor retina; likewise neither ICA nor ICV was significantly related to any ERG parameter at P30 and P60.
Conclusions::
Rod sensitivity in young ROP rats (P20) predicts blood vessel abnormality throughout development and into adulthood. In contrast, blood vessel tortuosity does not at any age predict neural outcomes in older ROP rats. In these longitudinal data, the temporal priority of SRod supports a causal role for the rod photoreceptors in the ROP disease process. Experimental manipulation of SRod in ROP rats is necessary to establish definitively the role of the rod photoreceptors in the pathogenesis of ROP.
Keywords: retinopathy of prematurity • electroretinography: non-clinical • imaging/image analysis: non-clinical