Could Diabetic Retinopathy be Prevented by Secretogranin III Inhibitors?
VASCULAR changes in diabetic patients can lead to long-term complications including diabetic retinopathy. Researchers from the Bascom Palmer Eye Institute, Miami, Florida, USA have discovered a new ligand called secretogranin III (Scg3) that possesses selective binding activity in diabetic blood vessels.
Diabetic retinopathy affects approximately 93 million people worldwide. An increase in retinal vascular leakage and inadequate neovascularisation can result in significant loss of vision. Current treatment involves administration of vascular endothelial growth factor (VEGF) inhibitors; however, success is only seen in around one-third of patients. Furthermore, VEGF inhibitors are contraindicated in newborn children. This means they cannot be used to treat retinopathy of prematurity (ROP), a condition also caused by abnormal neovascularisation, which affects up to 16,000 premature newborns each year in the USA.
Associate Prof Wei Li, Bascom Palmer Eye Institute, Miami, Florida, USA and colleagues designed a novel technique termed ‘comparative ligandomics’, enabling the identification of additional molecules involved in the regulation and modulation of blood vessels in diabetic mice. “Our ligandomics approach can be applied to any type of cell or disease to efficiently identify signalling molecules with pathogenic roles and therapeutic potential” stated Prof Li.
One of these newly identified molecules was Scg3; this ligand selectively bound to the vessels of diabetic mice, increasing vascular leakage and stimulating blood vessel growth, which was not seen in the control group. In comparison to Scg3, VEGF stimulated neovascularisation in both the diabetic and control mice.
Treating diabetic mice with Scg3-neutralising antibodies alleviated the retinal vascular leakage and also inhibited creation of new blood vessels in mice with oxygen-induced retinopathy, which is a commonly used animal model of human ROP. Prof Wei Li explained: “Scg3 inhibitors may offer advantages such as disease selectivity, high efficacy, and minimal side effects.” He added: “Because they target a distinct signalling pathway, anti-Scg3 therapies could be used in combination with, or as an alternative to, VEGF inhibitors.”
Currently the exact role of Scg3 in humans remains unconfirmed; however, this research is an exciting step towards determining whether Scg3-inhibitors could be an effective future treatment for diabetic retinopathy and ROP.