Glial cell metabolism is a potential new target for treating retinal degeneration

Retinopathy is a common cause of blindness and often occurs as a complication of metabolic diseases, including diabetes or mitochondrial disease. In retinopathy, leaking blood vessels in the light sensitive retinas of the eyes causes damage to retinal neurons, including photoreceptors, leading to vision loss.

The research group lead by  at the University of Helsinki Faculty of Medicine , , and  shows that removing a single protein important for mitochondrial maintenance, Twinkle helicase, in retinal glial cells is enough to cause full-blown neovascular retinopathy. Macroglia make up only around five percent of cells in the retina and previous studies of retinopathy in metabolic disease have focused on the neuronal cell types, overlooking a possible role of macroglia in driving retinal degeneration. 

“Our study reframes how we think about retinopathy: instead of glial cell malfunction being a consequence of the disease, this study shows it can be a primary driver”, says the doctoral researcher who led the study. The retina is a highly metabolically active tissue. Thus, defects of mitochondria, the cellular centers of metabolism, can compromise retinal function. The research group has previously highlighted the important role of the highly metabolically active glial cells in neurodegenerative disease. However, the removal of the same Twinkle helicase in glial cells of the brain cortex caused no damage to blood vessel despite equally dramatic effects on glial cells. “This tissue-specificity was not anticipated and suggests the retina has a unique dependence on glial mitochondrial health for vascular stability”, Olander continues.

Current treatments of retinopathy aim to slow down the loss of vision by targeting the abnormal blood vessels using antibodies against VEGF proteins. However, anti-VEGF therapies fail in many patients. “Our study pinpoints FGF2 and PGF, two other proteins that stimulate blood vessel formation, as potential new therapeutic targets for retinopathy”, says Suomalainen-Wartiovaara. “In addition, we identify retinal macroglia mitochondrial metabolism as a whole new therapeutic direction for treating retinopathy”, she continues. 

Despite severe vascular leakage, the neurons that carry visual information from the eye to the brain continued to function normally in the mice lacking mitochondrial Twinkle helicase in glial cells at the studied timepoint. “This is an important observation as it suggests that a therapeutic window exists before irreversible neuronal damage occurs”, Suomalainen-Wartiovaara summarizes. The finding brings hope for new approaches to treat retinopathy in diabetes or mitochondrial disease. 

The study was published in EMBO Molecular Medicine in May 2026.