Cone photoreceptor degeneration in the rd10 model of retinitis pigmentosa

Abstract

Purpose

Retinal pigmentosa (RP) is a heterogeneous group of retinal degeneration with a multitude of hereditary genetic defect. Photoreceptor degeneration usually starts with rods but invariably involves cones in later stages, leading to significant visual debilitation. Many animal models, in particular mouse models, have been used for the study of RP. The rd10 mouse, with mutation in the beta subunit of the rod phosphodiesterase gene, has been chosen as a model for an autosomal recessive form of human RP because of its later onset of retinal degeneration.

The topographic and morphological patterns of cone photoreceptor degeneration following the loss of rods were studied.

Methods

The rd10 mice were sacrificed and enucleated at postnatal 14 days, 21 days, 1 month, 2 months and 3 months. The retina was processed with immuno-staining to differentiate different photoreceptor cells and mounted flat for microscopic examination. The topographic pattern of cone photoreceptor loss at different ages was identified. Confocal microscopy was used to examine the morphological changes of cone degeneration. The retina from an adult c35 mouse was chosen as a reference for comparison.

Results

Following the onset of rod degeneration, the orderly arrangement of cones became disrupted. Remodeling of cone cells was observed as the loss of outer segments, swelling of the somata, and redistribution of opsin. Subsequently the inner segment and part of their axon and pedicles were involved. Some cones then demonstrated neurite sprouting, restoring a new polarized morphology. However, with increasing age, extensive atrophy of cone cells ensued. The topographic pattern of cone degeneration advanced from central to the peripheral retina, with the cones in the superior part of the retina most resistant to degeneration.

Conclusion

Cone photoreceptors respond to the loss of rods by remodelling and maintain a relatively normal phenotype for a considerable period of time, especially those in the superior part of the retina. This may provide a therapeutic window for cone rescue for patients of RP.