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Case and Cleveland Clinic researchers identify molecule in age-related macular degeneration

September 07, 2006
CLEVELAND-A dart-like molecule that adheres to proteins in the eye is the key that turns on the uncontrolled growth of blood vessels, according to researchers at Case Western Reserve University and the Cleveland Clinic Cole Eye Institute. Uncontrolled blood vessel growth is a major contributor to the development of age-related macular degeneration (AMD), the leading cause of blindness among people over 65 in the United States.

Robert Salomon and his graduate students Kutralanathan Renganathan and Liang Lu of Case's Department of Chemistry in the College of Arts and Sciences, found that the molecule, Carboxyethylpyrroles (CEPs), attaches to proteins found in the eye, triggering the uncontrolled growth of blood cells.

The Case researchers teamed up with Quteba Ebrahem Jonathan Sears, Amit Vasanji, John Crabb and Bela Anand-Apte and Xiaorong Gu (a Salomon group alumna), of Cleveland Clinic, to complete the study titled Carboxyethlpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration."

The results of their collaborative work were published in the recent Proceedings of the National Academy of Science (PNAS).

AMD is a progressive disease that results in the severe loss of vision. The early stages of AMD are characterized as "dry," with the disease advancing to the "wet form" as the retina, the part of the eye responsible for central vision, becomes infused with fluid from leaky new blood vessels, during a process called neovascularization. The unchecked blood vessel growth, or angiogenesis, in the retina accounts for 80% of the vision loss in the advanced stages of AMD.

The retina cells that detect light contain polyunsaturated fatty lipids that are exquisitely sensitive to damage by oxygen. Even in healthy eyes, these cells are renewed every ten days. The researchers at Case and Cleveland Clinic used a method developed by Salomon to specifically detect and measure the amount of CEPs found in the eye.

The researchers did in vivo animal studies with membranes from chicken eggs and rat eyes and found that CEPs attached to proteins induce angiogenesis. They also found that the protein part of CEP-protein adducts is not important for producing the growth of the blood vessels. Rather, the actual CEP is the cause of angiogenesis.

In an attempt to block CEP from triggering the angiogenesis process, "we are now trying to find the receptors - the keyholes - in the retina cells that are activated by CEPs," said Salomon. "We are also designing drugs that can mop up the CEPs or prevent their formation.\\\

Case Western Reserve University

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