correlation of retinal morphological and functional changes in a porcine model of inherited retinal degeneration

Abstract

Purpose: Retinitis pigmentosa (RP) is a group of inherited diseases that cause severe visual dysfunction due to the progressive degeneration of rod and cone photoreceptors. Inherited mutations in the rhodopsin gene are the most common causes of autosomal dominant RP, including the Pro23His substitution leading to protein misfolding. Although a Pro23His rhodopsin transgenic miniature pig model has recently been developed, the morphological correlation with functional changes remains limited. Herein, we addressed this issue using spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) in this experimental model.

Methods: Pro23His rhodopsin transgenic and wild-type hybrid pig littermates were obtained from the National Swine Resource and Research Center, University of Missouri-Columbia. Retinal morphology was assessed in vivo by SD-OCT between postnatal days (P) 30 and 120. Retinal function was evaluated using full-field ERG simultaneously (P30 to P120) in the same animal subjects. Morphological and ERG data were correlated with time in this porcine model of retinal degeneration.

Results: Retinal outer nuclear layer (ONL) thickness as measured by SD-OCT was significantly reduced (75%, p<0.05) at P60 in the transgenic pig compared to wild-type. A further reduction in ONL thickness occurred at P75 (86.6%, p<0.05), without significant change in ONL thickness between P75 and P120. The mean scotopic ERG a-wave and b-wave amplitudes (at a light stimulus of 3.0 cd·s·m^-2) decreased by 84.4% (p<0.05) and 77.6% (p<0.05), respectively between P30 and P90, with amplitudes remaining relatively stable between P90 and P120. The mean photopic ERG a-wave and b-wave amplitudes (at a light stimulus of 3.0 cd·s·m^-2) decreased by 62.4% and 60.4%, respectively between P30 and P90, with amplitudes remaining relatively stable between P90 and P120.

Conclusions: In this study, we correlated the in vivo morphological and functional changes over time (P30-P120) in a recently described porcine model of retinal degeneration. Our results are consistent with the previous findings, with the addition of novel in vivo data utilizing SD-OCT. These data provide a foundation for future studies investigating potential new therapeutic strategies to rescue photoreceptor degeneration.