Enzyme identified as therapeutic target for ocular neovascularization
By Dr. Tim Corson and Emily McKnight
A novel mechanism and possible treatment for ocular neovascularization has been identified by Dr. Tim Corson and colleagues, located on the Indiana University School of Medicine – Indianapolis campus.
Ocular neovascularization, the abnormal growth of new blood vessels in the eye, is a key component in much of the vision loss associated with multiple eye diseases, including retinopathy of prematurity, proliferative diabetic retinopathy, and “wet” age-related macular degeneration (AMD). Current drug therapies being used to slow the progression of ocular neovascularization target vascular endothelial growth factor, a single protein produced by cells that stimulates neovascularization; however, these therapies are not effective in all patients.
In an effort to better understand ocular neovascularization, Dr. Tim Corson, assistant professor of ophthalmology at IU School of Medicine, along with a team of researchers in the Corson Lab at the Eugene and Marilyn Glick Eye Institute and in collaboration with Gachon University College of Pharmacy, have identified the enzyme ferrochelatase (FECH) as a target of the antiangiogenic natural product cremastranone. FECH was increased in the eyes of both human and laboratory specimens undergoing ocular neovascularization. Chemical or genetic inhibition of FECH blocked proliferation, migration, and tube formation of retinal and choroidal endothelial cells in culture, as well as in an in vivo model of choroidal neovascularization as seen in wet AMD.
The well-known drug griseofulvin, used for treating fungal infections, inhibits FECH as an “off-target” effect. Dr. Corson’s team showed that griseofulvin could be used to block ocular neovascularization, raising the future possibility of repurposing this drug for use in the eye.
“Neovascular eye diseases like wet AMD are a major cause of debilitating blindness,” said Dr. Corson. “Our findings reveal an intriguing new molecular pathway for potential future drug development for these diseases, and also suggest that griseofulvin could be explored as an ophthalmic drug.”
This study was made possible with the support of several funding sources, including the NIH National Eye Institute; the International Retinal Research Foundation (IRRF); NIH National Heart, Lung and Blood Institute (NHLBI); Research to Prevent Blindness; the Retina Research Foundation; and more. For more information, please visit http://bit.ly/2orw7fP.
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