Blocking the Plasma Kallikrein Pathway Shows Promise as a Novel Diabetic Retinopathy Therapy

Diabetic retinopathy is a complex disease arising from disruption of multiple biological pathways. It is important to understand these pathways in order to target and develop new therapies for treatment. Diabetic retinopathy can lead to vitreous hemorrhages – leaking of small, or larger amounts of blood into the eye, which represent one mechanism by which the retina can be damaged. As retinopathy progresses, the likelihood of hemorrhage increases. Plasma kallikrein is a protein that has previously been shown to be elevated in diabetic retinopathy and appears to be a promising target for therapy. Dr. Feener and colleagues have identified plasma kallikrein as an important mediator of the damage caused by these hemorrhages and showed that blocking this pathway with a drug-like molecule reduces the consequences of hemorrhage, including leakage of retinal vessels and the related abnormal circulation.

Ramifications for Individuals with T1D:
Since the approval of ranibizumab (Lucentis) for diabetic macular edema, treatment options for diabetic eye disease have improved significantly. However, anti-VEGF therapies such as ranibizumab, do not work for everyone, and therapies are also needed to treat earlier stages of diabetic eye disease and prevent or reverse vision loss. If the ongoing work on plasma kallikrein inhibitors translates to clinical trials, this could represent a new treatment option for people with T1D and eye disease.

JDRF Involvement:
Dr. Feener’s findings are funded in part by a strategic research agreement from JDRF. JDRF has also partnered with a company, KalVista, who is developing small molecule inhibitors of plasma kallikrein with a focus on novel diabetic eye disease therapies. The KalVista work is currently at a preclinical stage.

Investigators and Institutions:
Dr. Edward Feener and colleagues, Joslin Diabetes Center.

Reference:
Liu J, Clermont AC, Gao BB, Feener EP. (2012) Intraocular Hemorrhage Causes Retinal Vascular Dysfunction via Plasma Kallikrein. Invest Ophthalmol Vis Sci. 2013 Feb 7;54(2):1086-94. doi: 10.1167/iovs.12-10537.