Investigators at the Lankenau Institute for Medical Research (LIMR), part of Main Line Health, showed that blocking the actions of a cellular protein called RhoB could limit diabetic retinopathy, macular degeneration and other diseases of the retina called retinopathies that impair or reduce vision.
These types of diseases share characteristic features, namely, inappropriate growths of blood vessels (called neovascularization) in the retina. Current treatments to ablate these blood vessels are not uniformly successful, leaving many patients at risk of progressive disease and blindness.
The researchers demonstrated in preclinical studies that administration of a novel monoclonal antibody to block the action of the protein RhoB resulted in reduced blood vessel growth in retinas, providing a rationale to develop the antibody as a therapy for retinopathies.
“We’re excited about these results because they serve as proof of concept on a therapeutic target to treat eye diseases that can have a devastating impact on patients’ quality of life,” said Lisa Laury-Kleintop, PhD, associate professor at LIMR and one of the authors of the new study. “The anti-RhoB antibody we used reduced neovascularization in the retinas of the animals we studied, and thus has the potential to limit the development of retinopathy.”
This line of work dovetails with basic research studies of RhoB — research pioneered in part at LIMR — where it was discovered that this protein drives neovascularization in tumors. Surprisingly, there is a similar process of pathogenic neovascularization in retinopathies. LIMR investigators suspect an immune connection of some kind, given recent findings that RhoB blockade using a similar approach can also arrest autoimmune diseases such as rheumatoid arthritis and lupus.
In their basic research, LIMR scientists had determined that blocking RhoB does not affect healthy cells, so the anti-RhoB treatment had few negative consequences in preclinical studies. However, when cellular stresses accumulate, as in cancer, autoimmune disease and now, as shown, in retinopathies, RhoB appears to increase the severity of these diseases — making it one of several disease-modifying proteins that LIMR scientists are investigating as potential therapeutic targets.
George Prendergast, PhD, president and CEO of LIMR, also was an investigator on the retinopathy study, as were researchers from the Lilly Research Laboratories in New York City. Their findings were published in the manuscript “RhoB antibody alters retinal vascularization in models of murine retinopathy” in Journal of Cellular Biochemistry. This study was supported by the Lankenau Medical Center Foundation and the Main Line Health System.