A new experimental study funded by the National Eye Institute shows that combination treatment using several already-approved drugs protects against photoreceptor degeneration in a mouse model.
The drugs, which are currently used for a range of conditions, from lowering blood pressure to treating prostate disease, may eventually offer an option for preventing vision loss associated with photoreceptor degeneration.
The researchers used transgenic mice with retinas highly sensitive to light-induced degeneration, along with wild-type mice, and exposed them to damaging levels of light. They found that after exposure, mice with light-induced retinopathy had reduced G protein coupled receptor (GPCRs) activity. Krzysztof Palczewski, Ph.D., chair of the Department of Pharmacology at Case Western Reserve University, and his team then identified available medications that activate GPCRs within the retina, and found 2 particularly effective combinations in which the drugs act on GPCRs through different pathways.
Both transgenic and wild-type mice that were given these treatments as a prophylactic therapy prior to exposure to blinding light showed better preservation of photoreceptors and surrounding tissue than those that did not.
Transcriptome analysis also revealed that mice treated with a combination therapy showed a lower magnitude of genetic response to the damage through upregulation and downregulation. “Interestingly, the combined lower doses of two drug treatments were able to reverse the gene expression changes induced by light-induced injury, and one of the combinations did not seem to induce the expression of undesirable genes,” said co-investigator Anand Swaroop, Ph.D.
The findings support the prospect of developing further treatments that use a systems pharmacology mechanism - where multiple drugs act on multiple pathways to affect a single target. The next step will be studies investigating dosing and toxicity risk when the agents are used together.
“It’s reassuring that the drugs used in the study are already being used in clinical practice, so we know their safety profile,” said Palczewski.
In future, these treatments could be applied for a myriad of retinal conditions including AMD and Stargardt disease.
“Discovering new uses for drugs that are approved by the FDA provides the quickest possible transition from bench to bedside,” said Neeraj Agarwal, PhD., manager of the NEI’s translational research program. “These studies are remarkable as they offer a systems pharmacologic approach for treating retinopathies.”