Bioengineering Studies of Transport Across Bruch's Membrane

Clinical lesions of early age-related maculopathy (ARM) involve Bruch’s membrane, a thin tissue layer between the small blood vessels in the choroid and the retinal pigment epithelium (RPE). It has been suggested that a decreased transport capacity of Bruch’s membrane, perhaps due to lipid accumulation, may be a critical early event in the pathogenesis of ARM. The decreased porousness of Bruch’s membrane may lead to RPE detachment. This proposal seeks to understand the structural changes in the extracellular matrix of Bruch’s membrane that accompany aging, and that could alter transport across the membrane. Dr. Johnson is using quick-freeze/deep-etch (QFDE) technology that will provide insights into the transport capabilities of Bruch’s membrane. QFDE preserves the extracellular matrix and allows structures to be visualized that are not seen in conventional transmission electron microscopy. Mathematical modeling is then applied to the images of Bruch’s membrane from QFDE analysis to evaluate the transport capabilities of Bruch’s membrane and to evaluate the importance of lipids in altering the transport. In this study, Dr. Johnson examines post-mortem, normal donor’s eyes over seven decades of life. The results from this experiment will establish a baseline of data for normal tissue, and Dr. Johnson’s future work will use diseased eyes. It is hoped that a better understanding of the pathophysiology of the early stages of ARM may help to guide the development of better treatments for the disease.

Grantee institution at the time of this grant: Northwestern University