Autosomal dominant rod-cone dysplasia in the Rdy cat 1. Light and electron microscopic findings

Abstract

Detailed morphological analyses, including retinal layer thickness studies, were performed on heterozygous affected cats with autosomal dominant rod-cone dysplasia (gene symbol Rdy). Abnormalities were evident in retinas from the earliest age examined (2 weeks). Both rod and cone photoreceptors were affected equally by the dystrophy which was characterized by retarded and abnormal development of the visual cells. Photoreceptor inner segments remained rudimentary and outer segments did not elongate normally. Outer segment material was sparse and consisted mostly of whorls of disorganized and disoriented disc lamellae. Photoreceptor cell synaptic terminals showed delayed and incomplete synaptogenesis. Degenerative changes were first observed at 4·5 weeks of age and were characterized by the appearance of pyknotic nuclei in the outer nuclear layer and displacement of photoreceptor cells into the subretinal space. Degeneration began in central retinal regions and proceeded towards the periphery, resulting in progressive loss of the photoreceptor cell layers. By 30 weeks of age only two to five rows of nuclei remained in the outer nuclear layer. Area centralis degenerative lesions in advanced affected eyes were characterized by focal absence of the retinal pigment epithelium and choriocapillaris and thinning of the underlying tapetum. Retinal autoradiography showed that in normal kittens aged between 4·5 and 11 weeks of age rod outer segment renewal rates varied between 2·49 and 2·79 μm per 24 hr. The failure to form a labelled band in retinal autoradiograms from Rdy-affected kittens most probably indicates defective rod disc morphogenesis. It appears that the genetic defect in Rdy cats permits retarded development of the photoreceptor cells, but becomes lethal when these cells begin functional differentiation.