Jason Miller, MD, PhD, University of Michigan
Mentor: Debra Thompson, PhD
Dr. Miller’s research program seeks to establish primary retinal pigment epithelium (RPE) culture models of dry age-related macular degeneration (AMD) as a platform for testing therapeutic interventions. RPE cells are those most affected in AMD.
With his 2020 AMDF/FFS Post-Doctoral Award ($11,250), he sought to identify non-toxic therapies for dry AMD:
“Our experiments involve stressing human RPE grown in the lab with a range of insults (including the insult of just carrying out routine daily activities but over a prolonged period of time), testing whether the RPE responds to the stress in a way that looks like the human disease. In particular, the cells on top of the RPE, called photoreceptors, undergo a daily shedding of their cell tip. These jettisoned fatty debris are cleared each day by the RPE. At the same time, lipid complexes enter the RPE from a set of tiny blood vessels underneath the RPE, called the choroid. These two lipid sources, photoreceptor tips and lipid particles from the blood stream, are an enormous burden to the RPE. Indeed, when the RPE loses its ability to efficiently clear this lipid load, the debris can accumulate inside and outside the RPE as ‘cellular trash,’ a first sign of dry AMD. The trash outside the cell is called ‘drusen.’ The trash inside the cell is called ‘lipofuscin,’ and it can eventually consume more than 50% of the cell’s volume.
To date, we have found an FDA-approved compound that turns on one of the cell’s ‘trash removal’ systems, termed autophagy, and non-toxically reduces lipofuscin accumulation and secretion of a major component of drusen, termed APOE. This drug may be a therapeutic candidate for dry AMD.”