The characterization of a new murine model of central areolar choroidal dystrophy showed that both cones and rods were affected by R195L mutation in peripherin‐2

Abstract

Aims/Purpose: Central areolar choroidal dystrophy (CACD) is a rare hereditary disease that leads to progressive retinal and choriocapillaris degeneration and vision loss. In Spain, there is a family suffering this disease, since they carry the mutation p.Arg195Leu in PRPH2. Our team have generated a mouse model of CACD carrying the same mutation as the Spanish patients. Our aim was to characterize the progression of CACD in the retina structurally and morphologically in this new murine model.Methods: We studied the model C57BL/6J‐Prph2em1Sal by electroretinography, optomotor test, optical coherence tomography (OCT), immunofluorescence, confocal microscopy, and transmission electron microscopy (TEM) to assess the structural and morphological alteration of the retina during the progression of the disease in Prph2WT/WT, Prph2WT/KI, and Prph2KI/KI mice.Results: A progressive retinal degeneration was found affecting the retina of both Prph2WT/KI and Prph2KI/KI mice models. We observed a significantly decreased retinal function from 3 months of age in Prph2KI/KI and 6 months of age in Prph2WT/KI, that was correlated with a progressive degeneration of the outer nuclear layer (ONL) shown by OCT images. The Prph2KI/KI mice showed a degeneration of photoreceptors with a reduction in the ONL thickness from 3 months of age, and a severe decrease in the number of photoreceptor rows at 6 months of age. The Prph2WT/KI, however, showed a slower decrease in the ONL thickness, starting from 6 months of age. Additionally, we found unstructured and shortened photoreceptor outer segments as evidenced by immunofluorescence against peripherin, rhodopsin and cone‐arrestin. Moreover, TEM images confirmed an abnormal stacking of photoreceptor discs.Conclusions: The generated model is useful for the study of CACD. Moreover, the p.Arg195Leu mutation in PRPH2 causes the alteration of the outer segments first, triggering the degeneration of both cones and rods.