Abstract
Abstract: :
Purpose:To characterize the course of retinal disease in XLPRA2, a canine model of early onset XLRP caused by a 2 nucleotide deletion in exon ORF15 of the RPGR gene that results in a frameshift and a toxic gain of function. Methods:Retinas from 21 dogs (9 males, 8 homozygous females, 4 carrier females) were examined. The tissues were fixed, dehydrated, embedded in epoxy resin, sectioned at 1 µm, and stained with azure II/methylene blue and PPDA counterstain. Sections were observed under light microscopy, and the cytologic characteristics as well as the topographic distribution of the disease were determined. Results:Abnormal development of photoreceptors was recognizable as early as 27 days of age by misalignment of their outer segments. This was followed by disorientation and disorganization of photoreceptor outer segments. At a later stage, outer segment fragmentation resulted in clusters of discs scattered throughout the RPE/ inner segment interface. Reduction in length and broadening of rod and cone inner segments was next observed, accompanied by an increased number of pyknotic nuclei in the ONL. By 6 months of age the ONL width had decreased by about 50%. Disease was observed throughout the length of the retina, but was more advanced in the periphery. Carrier females showed both a generalized reduction in ONL thickness overall, and focal areas of more severe retinal degeneration consistent with random X–chromosome inactivation. Conclusions:XLPRA2 is an early onset model of XLRP that is morphologically characterized by abnormal rod and cone development followed by progressive photoreceptor degeneration.
Keywords: retinal degenerations: cell biology • pathology: experimental • cell death/apoptosis