PKal May Join VEGF as DME pathway
A protein called PKal (plasma kallikrein) and its associated molecules are key players in an inflammatory molecular pathway involved in diabetic macular edema, according to a study published in Diabetes.
A protein called PKal (plasma kallikrein) and its associated molecules are key players in an inflammatory molecular pathway involved in diabetic macular edema, according to a study published in
Researchers at the Joslin Diabetes Center, Harvard Medical School, Boston, and the Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, noted that anti-VEGF therapies have greatly improved the treatment options for DME in recent years, but only about one-half of DME patients are fully responsive to these new therapies.
Research in the lab of Edward P. Feener, Ph.D., an investigator in the Section on Vascular Cell Biology and director of the Proteomics Core, Joslin Diabetes Center, and an associate professor of medicine at Harvard Medical School, has shown that a substantial percentage of patients with DME do not have high levels of VEGF in their vitreal fluid, but do have high levels of a PKal.
The scientists then demonstrated in animal models that the PKal molecular pathway can induce retinal edema through mechanisms that are independent of the VEGF pathway.
The discoveries boost the evidence that agents targeting PKal eventually may be useful in treating DME that is not fully responsive to VEGF inhibitors.
“Although anti-VEGF therapies have proved effective in some people with [DME], additional therapies are needed to complement existing ones and to treat individuals who do not respond to currently available therapies,” said Helen Nickerson, Ph.D., director of Translation Research at the Juvenile Diabetes Research Foundation (JDRF), which helped support Dr. Feener’s research. “Dr. Feener’s work is critical in elucidating one such potential target for a new DME therapy.”
In the study, the researchers examined samples of vitreous fluid from 61 patients with diabetic retinopathy or a control group with a non-diabetic form of macular damage. They found that that the DME patients fell into two groups: one with high levels of both PKal and VEGF proteins, and the other with high levels of PKal but not VEGF.
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