Cellular Scale Measures of Short-Term Retinal Atrophy Progression

This project will measure the short-term cellular changes that occur prior to irreversible retinal atrophy in people with pentosan polysulfate sodium toxicity.

The aim of this study is to determine biomarkers of short-term progression of outer retinal atrophy within the transition zone between healthy and atrophic retina. Towards this goal, we will measure how the retinal pigment epithelium, a layer of cells vital to photoreceptor health and a primary sight of AMD pathology, changes shape and density as retinal atrophy progresses in pentosan polysulfate sodium toxicity (Aim 1). We will simultaneously measure cone photoreceptor density and single cone responses to light within the transition zone as underlying RPE cells change (Aim 2).

Severe dry AMD is difficult to study with adaptive optics technology due to the highly variable nature of the disease, poor vision and the age-related changes of the eye. We will overcome these barriers by studying biomarkers of atrophy progression in pentosan polysulfate sodium toxicity, a recently identified cause of rapidly progressive retinal atrophy similar to dry AMD. This project will also use adaptive optics optical coherence tomography (AO-OCT), an innovative technology, to image in vivo cellular scale imaging of the RPE and cone photoreceptors in 3D.

Results from this study could provide prognostic biomarkers of impending retinal atrophy progression. These biomarkers are needed to determine which patients with age related macular degeneration are likely to have quick disease progression and the most likely to benefit from novel drug development to slow and stop the devastating visual effects that occur with geographic atrophy.