Mark Johnson, Ph.D.
Northwestern University
Evanston, Illinois
Project: Bioengineering Studies of Transport Across Bruch’s Membrane

Bruch's membrane is a thin connective tissue layer that lies between the eye’s choriocapillaris (minute blood vessels of the choroid layer) and the retinal pigment epithelium. Since the transport of nutrients to the retina and the disposal of waste products must pass through Bruch's membrane, the obstruction of transport through this tissue can have serious physiological consequences. It is known that the early stages of age-relate macular degeneration (AMD) are characterized by minor to moderate vision loss that is associated with debris accumulation, particularly the accumulation of lipids. Dr. Johnson and his colleagues are exploring the hypothesis that this accumulation of debris impairs the transport capacity of Bruch's membrane, leading to a progressive worsening of the condition. Because the only known risk factor for the early stages of macular degeneration is advanced age, it is important to understand how age-related changes in Bruch's membrane may predispose some individuals for lesion development. Dr. Johnson is using a bioengineering technique called quick freeze/deep etch to examine how the transport capacity of Bruch's membrane changes with age. The results of this study are expected to provide a firm quantitative basis for understanding the transport properties in Bruch's membrane of eyes that have macular degeneration, leading to the development of better treatments or even a means of preventing AMD. This project is a continuation of a Macular Degeneration Research study initiated in 2001.

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Janet R. Sparrow, Ph.D.
Columbia University
New York, New York
Project: Macular Degeneration: The Role of A2E in RPE Atrophy

It has long being suspected that macular pigments composed of the carotenoids lutein and zeaxanthin protect the retina both by filtering high energy blue light and by serving an antioxidant function, but the specific photochemical reactions that these nutrients protect against remain unknown. Dr. Sparrow has proposed that the lutein and zeaxanthin in retinal pigment epithelium (RPE) cells protect against the light-induced oxidative changes (photoxidation) of an aging fluorescent compound (A2E), which accumulates in these cells. She has also hypothesized that lutein and zeaxanthin suppress similar photooxidative changes in the A2E precursor molecule, called A2-PE. In earlier work, she demonstrated that the excitation of A2E with blue light leads to the generation of singlet oxygen and that these reactive oxygens are subsequently inserted into the A2E molecule (photooxidation) creating a very reactive derivative with the potential for damaging cellular macromolecules such as protein and DNA. Her goal now is to demonstrate that the precursor A2-PE undergoes the same photooxidative change, and to determine whether lutein and zeaxanthin protect against the photooxidation of A2E and A2-PE. Then her team will test the assumption that these carotenoids prevent photoxidative changes in A2E and A2-PE through their ability to deactivate the highly reactive oxygen species (singlet oxygen). They will compare lutein and zeaxanthin’s antioxidant capabilities and determine whether these nutrients can act in synergy with vitamin E and vitamin C, other natural antioxidants that are present in these cells. The long-term goal of this work is to develop therapies that would counteract the photochemical events initiated by A2E. This project is a continuation of an MDR-funded study began in 2001.

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