Steve Chaplin, 812-856-1896
Indiana University, IU Communications
Jeremy Craig, 404-413-1357
Georgia State University, University Relations
BLOOMINGTON, Ind. and ATLANTA – A team of researchers, including a GSU mathematics professor, have learned more about the mechanisms of a disease that robs the elderly of their sight, which will help lead to better treatments against it in the future.
Yi Jiang, associate professor of mathematics and statistics at Georgia State, was part of a team led by Abbas Shirinifard, a postdoctoral researcher at Indiana University, that developed new computational models for a stage in the process of a severe form of age-related macular degeneration called choroidal neovascularization, or CNV.
The results were recently published in the Public Library of Science journal PLoS Computational Biology.
A more severe form of age-related macular degeneration, known as neovascular or “wet” AMD, arises when new blood vessels, during the process known as CNV, grow under the center of the retina, which is called the macula. These vessels can leak fluid, bleed and cause scar formation destroying vision in as little as three months.
“AMD is the main cause of vision loss in the elderly and is a looming epidemic in our aging society,” Jiang said. “Presently, there’s no way to tell if a patient’s eye will develop AMD or which form of AMD, nor effective treatments for AMD, mainly because we do not understand the cause of AMD or CNV.
“This modeling study shows a completely novel way of thinking about CNV,” she added. “If the new hypothesis is validated by experimental and clinical studies, it could have a very significant impact on the treatment of AMD.”
One current treatment for CNV either kill the invading blood vessels with drugs injected into the eye, which also damages the retina and kills needed blood vessels. The other involves laser-heating the blood vessels, which can cause damaging retinal scars. Neither treatment still addresses the underlying problems that cause the blood vessels to invade, so relapses are common and many patients still lose vision within a year or two.
The modeling performed at IU, with the aid of Jiang, will help lead to better treatments for the illness.
The study uses mathematical and computational modeling to point out that adhesion strength between cells in the eye, and various anatomical layers in the central retina, is key to keeping blood vessels where they should be.
“The complex structure of the retina meant that many types of adhesion could be important,” Shirinifard said, “the three most prominent being between the pigmented retinal cells [the black lining of the eye] and Bruch's membrane [the substrate that supports the retina], between adjacent pigmented retinal cells, and between pigmented retinal cells and the overlying photoreceptors.”
Co-authors on the paper with Shirinifard and IU’s Biocomplexity Institute Director James Alexander Glazier were associate scientists Maciej Swat and J. Scott Gens, both of the Biocomplexity Institute and the IU Department of Physics; Fereydoon Family and Hans E. Grossniklaus, of Emory University; and Jiang of GSU.
Jiang advised Shirinifard, guided him through the mathematical model development and interpretation of simulation results.
“We were able to model the interactions of different degrees of impairment of each type of adhesion and the variation from case to case,” Shirinifard said. “Amazingly, these simulations were able to replicate the complex spectrum of CNV seen in the clinic.”
The article is Shirinifard A, Glazier JA, Swat M, Gens JS, Family F, et al. (2012) "Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study." PLoS Comput Biol 8(5): e1002440. doi:10.1371/journal.pcbi.1002440 .
May 15, 2012