Combinations of Approved Drugs Could Prevent Light-Induced Retinopathy

Multiple medications that target G protein coupled receptors could prevent disease-related visual impairment.

Combining FDA-approved medications can potentially protect against cell loss caused by retinal diseases in mice.

Researchers found various medications that treat various conditions, such as high blood pressure and prostate disease, could protect against degeneration of retina cells, according to a study published by Science Signaling.

This type of cell loss is associated with age-related macular degeneration and Stargardt disease. If their treatment is successful, researchers believe it could prevent visual impairment. Drug combinations acted on G protein coupled receptors (GPCRs), which keep the cells in homeostasis when functioning properly.

Researchers analyzed wildtype mice, and mice that were bred to have retinas susceptible to light-induced photoreceptor degeneration, according to the study. Both types were exposed to bright light until it caused photoreceptor degeneration, thinning of the retinal layer, and a loss of other retinal cells.

In previous studies, researchers found that light-induced retinopathy hindered GPCR activity. Researchers then identified more than a dozen drugs that appeared to be protective against light-induced photoreceptor degeneration. In the current study, they identified 2 combinations of drugs that optimize GPCR activity in different ways.

Both types of mice were likely to preserve their photoreceptors and retinal layers if they received the drug combinations prior to light exposure, compared with mice who did not receive the treatment, according to the study. Then, researchers performed transcriptome analysis to analyze the effect on a molecular level.

“Light-induced injury to the cells of the retina can trigger the upregulation or downregulation of over 100 genes as the cells attempt to respond to the damage," said study co-investigator Anand Swaroop, PhD. “Studying these gene expression patterns is a far more sensitive marker of retinal degeneration than looking at structural changes to the cells under a microscope.”

This pharmacology approach uses multiple medications that all utilize different biological pathways to reach the same target; therefore, smaller doses of the medication can be used to reduce side effects.

"Interestingly, the combined lower doses of 2 drug treatments were able to reverse the gene expression changes induced by light-induced injury, and 1 of the combinations did not seem to induce the expression of undesirable genes," Dr Swaroop said.

While the side effects of these drugs are already known, further studies are needed to explore any potential risks of toxicity for combining the treatments.

“It's reassuring that the drugs used in the study are already being used in clinical practice, so we know their safety profile,” the study's principal investigator, Krzysztof Palczewski, PhD, concluded.