Retinal Histopathology in Eyes from a Patient with Autosomal Dominant Retinitis Pigmentosa caused by the Pro23His Rhodopsin Mutation

Abstract

Purpose: : To evaluate the histopathology in donor eyes from a patient with autosomal dominant retinitis pigmentosa (adRP) caused by a Pro23His rhodopsin mutation.

Methods: : Eyes were obtained from a 72 year-old male who died from a stroke secondary to subdural hematoma. Eyes were fixed in 4% paraformaldehyde and 0.5% glutaraldehyde in PBS within 17.5 hours postmortem. Globes were evaluated with macroscopic, SLO and OCT imaging. Macula and peripheral regions were processed for electron microscopy and immunocytochemistry. Three age-matched normal eyes were used as controls. DNA was obtained from blood and buccal samples of the donor, his affected daughter and son. Direct genomic sequencing of the entire rhodopsin coding region and flanking intronic sequences was performed.

Results: : DNA analysis of the donor and affected family members revealed a rhodopsin Pro23His mutation. All imaging modalities revealed peripheral areas of heavy bone spicules. The area surrounding the optic nerve showed evidence of RPE atrophy as choroidal vasculature could be visualized. The fovea and optic nerve could be clearly identified with OCT. Histology revealed a highly degenerate retina with little evidence of stratified nuclear layers in all peripheral areas studied. In contrast, a prominent outer nuclear layer was present in the perifoveal region. The RPE was reduced from normal thickness in the macula and thin and discontinuous in the far periphery. Bone spicule pigmentation was extensive, and present throughout the degenerate retina in the periphery, usually associated with blood vessels. Cones labeled with opsin and arrestin antibodies were present in the macula, but were mostly absent from the periphery. Cone synapses and outer segments were not observed. A few highly disorganized, rhodopsin labeled rods were detected in the macula but were absent in the periphery. Calbindin labeled second order neurons were unevenly distributed in the periphery.

Conclusions: : The histopathology of the retina in a patient with advanced Pro23His rhodopsin mutation displayed highly degenerate peripheral retina and preservation of some cone and rod photoreceptors in the macula.

Keywords: retinal degenerations: cell biology • immunohistochemistry • genetics