Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration

This protocol enables new treatments and preventions for age-related macular degeneration or AMD. This is the largest disease with a central neurodegeneration and yet we think it’s the most approachable because of the precise structure of the eye and the availability of cellular-level clinical imaging of the retina. The neovascular complications of the underlying disease of AMD have been treated successfully for 15 years in the 15%of patients who have it.

Recently, the FDA approved the first drug for the end stage of the underlying disease. Single-cell RNA sequencing has revealed the molecular repertoire of the 100-plus cell types in the retina and supporting choroidal vasculature. Eye-tracked optical coherence tomography or OCT has enabled us to glimpse a detailed cellular-level progression sequence in the clinic.

Existing cell and animal model systems for AMD research are non-predictive of human pathology and progression risk. This impedes the development of new treatments and preventions. Our lab contributed many top-level findings about AMD, including the early loss of broad photoreceptors required for night vision.

It was also observed that better preserved maculas with attached neurosensory retinas are directly relevant to clinical OCT imaging. Many parts of AMD pathology became visible with clinical OCT which shows cross-sectional views of the retina and choroid. The OCT results of human donor eyes can be directly compared to findings in clinical imaging.

If laboratories could emulate clinical imaging standards by using OCT to characterize eyes before assays and laboratory findings like gene expression or proteomics and leverage the longitudinal timeline of clinical imaging to focus on the most informative risk indicators.