Autosomal Dominant Retinitis Pigmentosa Caused by the Threonine-17-Methionine Rhodopsin Mutation: Retinal Histopathology and Immunocytochemistry

Abstract

The retinas from a 68-year-old man with autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation were studied. Patients with this mutation have a characteristic clinical phenotype that shows intra- and interfamilial consistency. The retinas were examined by light and electron microscopy, including immunocytochemistry with markers for rods, cones, the retinal pigment epithelium, the interphotoreceptor matrix and Müller cells, and the results were correlated with those from visual function tests performed fourteen months before death. Grossly, both retinas had heavy deposits of bone spicule-like pigmentation inferiorly, but the superior retinas showed much less pigmentation. The maculas contained no rods and an incomplete monolayer of cone somata, consistent with the patient's severely reduced central vision. The inferior retinas contained no rods and rare cone somata, correlating with an absolute scotoma in the superior held. The superior retinas had near-normal-appearing rods and cones in the far periphery and a gradient from the midperipheral to central retina of progressively shortened outer segments and loss of photoreceptors, consistent with the patient's reduced rod and cone electroretinograms and retained rod and cone sensitivities in the inferior peripheral held by perimetry. Immunocytochemistry with rod-specific markers was qualitatively normal in the superior mid to far peripheral retina. Electron microscopic immunogold labeling with anti-rhodopsin revealed similar densities of gold particles over rod outer segments of the RP and a normal donor retina. Degenerate photoreceptors in the superior equatorial region of the RP retina had short outer segments, and some rods had surface labeling with anti-rhodopsin of the inner segments, somata and synapses. The results indicate regional retinal differences of disease severity in this genotype and that rods in the superior peripheral retina have normal morphology despite the presence of the mutant allele. To the authors' knowledge, this is the first detailed study of rod photoreceptors in the retina of an RP patient with a rhodopsin mutation. © 1994 Academic Press. All rights reserved.