Investigating Vascular Changes in the Eye
Diabetes is the leading cause of blindness in people ages 20 to 74 in the United States. To determine how diabetic eye disease develops and to find strategies to preserve vision, researchers in the Section on Eye Research conduct molecular, biochemical, cellular and clinical studies.
Diabetic retinopathy (eye disease) results in visual loss though two main mechanisms. In one condition, diabetic macular edema (DME), the small blood vessels of the retina leak fluid into the macula in the center of the retina, impairing vision. In the other condition, proliferative diabetic retinopathy (PDR), blood vessels in the retina grow where they should not.
Researchers in the section conduct studies to understand the basic molecular mechanisms underlying retinal vascular disease—in particular, the activity of growth factors in PDR and DME—and use results to design animal and clinical trials, which are now investigating the effects of oral protein kinase C inhibitors, growth factor inhibitors, antioxidants and anti-proliferative agents.
In pioneering work, researchers defined the role of vascular endothelial growth factor (VEGF), hepatocyte growth factor, pigment epithelial-derived factor and others, and tested novel inhibitors of these pathways in cells, animals and humans. In addition, they identified new areas on the genes that control the expression of these molecules. Further studies show that the stretching of blood vessels during high blood pressure alters the expression of these factors—findings that may lead to future treatments for diabetic retinopathy exacerbated by hypertension.
Researchers also study the role of genes in promoting the progression of diabetic eye disease and whether antioxidants, such as vitamin E, can normalize retinal blood flow and thereby slow or reverse vascular changes.
Novel Imaging Techniques
The section is internationally recognized for its expertise in novel imaging methods. The eye is unique in that its vasculature, microvasculature and neuronal systems can be visualized directly in vivo, enabling noninvasive evaluation of biological processes. For example, a retinal imaging system called the Joslin Vision Network (JVN) uses a combination of video cameras and computers to image the back of the eye without dilating the pupil. These stereoscopic color images compare favorably with a retinal specialist exam, and can accurately diagnose retinopathy long before symptoms appear and in locations where access to ophthalmology care may be limited. JVN is deployed in more than 70 sites in 20 states. Surprisingly, in more than 50 percent of patients with diabetes who do not have retinopathy, the JVN identifies eye disease that needs evaluation.
The section also collaborates with the creators of an innovative imaging device called the ultra high-resolution ocular coherence tomogram, which provides a cross section of the retina revealing individual cell layers. Researchers are evaluating these images to determine if they provide additional or earlier information about patients who have or may develop eye disease.
Collaborating for a Cure
Building on their earlier findings—that VEGF is elevated in retinal and ocular fluids in people with diabetic retinopathy—investigators are collaborating with colleagues in the Section on Vascular Cell Biology to determine which factors regulate VEGF expression in the eye and how vascular wall stretching affects its regulation. Another collaboration involves studies of protein kinase C inhibitors to determine whether they can slow the progression of diabetic retinopathy, reduce macular edema and/or preserve vision. A further collaboration, which also includes Beth Israel Deaconess Medical Center, is evaluating whether changes in electrophysiology of the eye can help in the detection of early or incipient diabetic neuropathy (nerve damage).
The collaborative approach is also undertaken at the national level via the Diabetic Retinopathy Clinical Research Network, a National Eye Institute-sponsored network of over 100 U.S. sites dedicated to rigorous clinical trials of new therapeutic approaches for diabetic retinopathy and diabetic macular edema. A member of the section is the founding Network Chairman for this initiative.