Interspecies Correlations between Human and Mouse <i>NR2E3</i>-Associated Recessive Disease.

Abstract

<i>NR2E3</i>-associated recessive disease in humans is historically defined by congenital night blinding retinopathy, characterized by an initial increase in short-wavelength (S)-cone sensitivity and progressive loss of rod and cone function. The retinal degeneration 7 (<i>rd7</i>) murine model, harboring a recessive mutation in the mouse ortholog of <i>NR2E3</i>, has been a well-studied disease model and recently evaluated as a therapeutic model for <i>NR2E3</i>-associated retinal degenerations. This study aims to draw parallels between human and mouse <i>NR2E3</i>-related disease through examination of spectral domain optical coherence tomography (SD-OCT) imaging between different stage of human disease and its murine counterpart. We propose that SD-OCT is a useful non-invasive diagnostic tool to compare human clinical dystrophy presentation with that of the <i>rd7</i> mouse and make inference that may be of therapeutically relevance. Additionally, a longitudinal assessment of <i>rd7</i> disease progression, utilizing available clinical data from our patients as well as extensive retrospective analysis of visual acuity data from published cases of human <i>NR2E3</i>-related disease, was curated to identify further valuable correlates between human and mouse <i>Nr2e3</i> disease. Results of this study validate the slow progression of <i>NR2E3</i>-associated disease in humans and the <i>rd7</i> mice and identify SD-OCT characteristics in patients at or near the vascular arcades that correlate well with the whorls and rosettes that are seen also in the <i>rd7</i> mouse and point to imaging features that appear to be associated with better preserved S-cone mediated retinal function. The correlation of histological findings between <i>rd7</i> mice and human imaging provides a solid foundation for diagnostic use of pathophysiological and prognostic information to further define characteristics and a relevant timeline for therapeutic intervention in the field of <i>NR2E3</i>-associated retinopathies.