A New Animal Model of Severe Age-related Macular Degeneration
MentorOrson Moritz, PhD
To determine the role of deposits of cellular debris termed reticular pseudodrusen (RPD) in the development of severe forms of age-related macular degeneration. This study will explore the origins of cellular debris deposits in the retina and determine why they are correlated with vision loss. I will use a CRISPR-modified frog model with a mutation that affects photoreceptor structure. The photoreceptors slowly break down, and then the cellular debris appears, similar to what happens in an aging eye. I will determine the composition of these deposits using MALDI imaging mass spectrometry to determine novel therapeutic targets. I will test treatments that prevent the accumulation of these deposits to see whether vision is preserved.
Animal models allow us to study human disease in an environment that is impossible to mimic using cell lines or retinal cultures. Until the discovery of RPD-like deposits in my prom1-null frogs, there was no approachable animal model of RPD and geographic atrophy as a result of age-related macular degeneration. The results from this research project will further our knowledge of RPD development and verify the role of RPD as a biomarker and a risk factor for severe progression of age-related macular degeneration. This research project is relevant to human disease in that it will further our knowledge of RPD development, establish RPD as a risk factor for severe AMD, and provide visual health practitioners plausible and identifiable biomarkers that can be detected during routine eye examinations. In addition, this project will inform treatment for patients with significant size or numbers of RPD in the form of minor changes in diet or lifestyle that will prevent or slow progression to visual impairment and blindness, leading to significantly improved outcomes for aging populations.