New pathway for diabetic retinopathy treatment found

Researchers have identified a new link between diabetes and sight loss that has the potential to lead to new treatments for diabetic retinopathy (DR).

According to new research published in The American Journal of Pathology high levels of glucose increases the levels of enzymatic precursor – lysyl oxidase propeptide (LOX-PP) ­­– that promotes cell death.

“We found that hyperglycemic and diabetic conditions increased LOX-PP levels,” Dr Sayon Roy, professor of medicine and ophthalmology at Boston University School of Medicine and lead investigator on the study, said.

“LOX-PP may induce cell death by compromising a cell survival pathway, and in retinas of diabetic rats, increased LOX-PP contributed to retinal vascular cell death associated with DR. Administration of recombinant LOX-PP alone was sufficient to induce cell death. This report shows novel functionality of LOX-PP in mediating cell death under high glucose condition in retinal endothelial cells as well as in diabetic animals.”

Researchers administered artificially synthesised LOX-PP in both normal and diabetic rats and examined the changes associated with DR such as swelling, blood vessel leakage, changes to vascular walls and histologic indicators.

In the retinas of diabetic rats, more acellular capillaries (AC) and greater pericyte loss (PL) was observed when compared to contrail group. Among non-diabetic rats administered LOX-PP, increased AC and PL was also observed.

The team behind the project noted that there is a clear connection between high glucose and LOX-PP levels, which in turn promotes cell death. Additionally, LOX-PP seems to compromise a pathway involved in cell survival.

“DR is the leading cause of blindness in the working age population,” Roy said. “Unfortunately, there is no cure for this devastating ocular complication. Our findings suggest a novel mechanism for high glucose-induced cell death involving LOX-PP, which may be a therapeutic target in preventing retinal vascular cell loss associated with DR.”