Rapid photoreceptor degeneration in the area centralis and visual streak of Rpe65-deficient dogs: morphologic and histologic characterization

Abstract

Purpose: An early and marked thinning of the retina develops in the area centralis and visual streak in our colony of Rpe65-deficient dogs. This is not solely explained by the early S-cone loss we have already described in this model. We sought to characterize the loss of photoreceptors in this region in more detail.

Methods: We utilized fundus photography and SD-OCT to evaluate the lesion in vivo in Rpe65-deficient dogs. Following euthanasia, eyes were collected and examined using light microscopy and immunohistochemistry on retinal wholemounts and sagittal retinal sections. Rod and cone specific photoreceptor antibodies and inner retinal markers were utilized in immunohistochemistry.

Results: An ophthalmoscopically visible degenerate lesion was present in the area centralis and was first identifiable in dogs from 6-weeks old. The lesion increased in size with age, and the visual streak also became involved. This correlated with a marked thinning of the outer retinal layer as seen on OCT. Histologically, both S- and LM- opsin positive cone photoreceptors were significantly depleted in the visual streak and virtually absent within the area centralis; rods were also moderately depleted within the same areas.

Conclusions: We consistently found substantial and progressive loss of photoreceptors within the area centralis and visual streak in our Rpe65-deficient dog colony. Similar changes have not been reported in other colonies of Rpe65-deficient dogs, possibly indicating the influence of background genetic effects. This study shows that there is a marked loss of cones, but also rods from this region. The area centralis and visual streak have the highest density of photoreceptors in the canine retina. Competition for residual low levels of retinoids (other than 11-cis-retinal), that may allow for the residual bright light vision in these dogs, could make this region at greater risk of photoreceptor death than lower-density regions.

Keywords: 696 retinal degenerations: hereditary • 648 photoreceptors