Dysregulation of the OGF-OGFr pathway and associated diabetic complications

Diabetes is a worldwide epidemic with more than 550 million individuals expected to be diagnosed with the disease by 2030. Complications associated with diabetes affect nearly all systems, but more than 54% of diabetic individuals have ocular surface disorders including keratopathy, dry eye or altered corneal surface sensitivity, and nearly 70% experience slow healing foot ulcers which if left untreated, can lead to amputation. There is new information regarding the underlying pathophysiology associated with these complications, as well as potential treatment.

This commentary assembles data on preclinical studies showing that corneal surface complications such as dry eye and sensitivity, as well as delayed epithelial wound healing in the cornea and skin in diabetic rats and mice, correlate with a dysregulation of the opioid growth factor (OGF)-opioid growth factor receptor (OGFr) regulatory axis. The peptide in this pathway, OGF, chemically termed [Met⁵]-enkephalin, is elevated in the serum of humans and animals with either type 1 or type 2 diabetes. The cause for this finding is unknown. However, there are studies that demonstrate that blockade of the interactions between OGF (or elevated levels of OGF) and its receptor can reverse and, in some cases, prevent the onset of diabetic corneal complications. Clinicians and healthcare workers need to recognize this fundamental pathophysiology leading to diabetic complications.

Dysfunction of the OGF-OGFr growth regulatory system plays a role in the development of ocular surface complications and delayed cutaneous wound healing complications in multiple animal models of both Type 1 and Type 2 diabetes. Modulation of this system may hold promise for reversing or even preventing these diabetic complications in humans. Moreover, monitoring serum levels of OGF should be investigated as an indicator of the development of these and other diabetic complications.