Reserpine has potential to be repurposed as treatment for retinitis pigmentosa, studies suggest

In the latest study, researchers evaluated the therapeutic potential of reserpine for autosomal dominant retinitis pigmentosa. Image credit: AdobeStock/thanarak/AI

New studies supported by the National Institutes of Health’s (NIH) National Eye Institute (NEI) Intramural Research Program suggest that the drug reserpine, approved for high blood pressure in 1955, has the potential of treating retinitis pigmentosa in the form of a small molecule therapy. Currently, no therapy exists for the inherited retinal disease (IRD).¹ The studies were published in a singular report in eLife, according to a news release.

“The discovery of reserpine’s effectiveness may greatly speed therapeutics for retinitis pigmentosa and many other inherited retinal dystrophies, which can be caused by one of more than a thousand possible mutations affecting more than 100 genes. Reserpine’s neuroprotective effect is independent of any specific underlying gene mutation,” said the study’s lead investigator, Anand Swaroop, PhD, senior investigator at NIH’s National Eye Institute, in the release.

In the latest study, researchers evaluated the therapeutic potential of reserpine for autosomal dominant retinitis pigmentosa, a dominant form of the disease caused by a mutation in the visual pigment gene rhodopsin, by using a P23H-1 rat model and performing a series of assays to evaluate the response to reserpine treatment on retinal pathology. Reserpine was administered via intraperitoneal injection, with data collected through optokinetic tracking; ERG recordings; fundus imaging and optical coherence tomography; immunohistochemistry; RNA extraction and library preparation; and RNA-seq and data analysis.²

Evidence from the studies showed that reserpine improves survival of photoreceptor cells, the light-detecting retinal neurons that die due to retinitis pigmentosa and other retinal dystrophies. Compared to untreated rates, reserpine preserved the process in which photoreceptors convert light that enters the eye into electrical signals that are sent to the brain to produce vision, known as phototransduction, in rod photoreceptors.¹ “The neuroprotective effect of reserpine was achieved, at least in part, through the restoration of the balance between autophagy and the ubiquitin-proteasome system, the stress-response pathways maintaining cellular proteostasis,” the study authors stated.

Additionally, reserpine produced better protective effects for rod photoreceptors in female rats in comparison to male rats. Researchers also noted that significant preservation of cone photoreceptors was found more often in female rats compared to male rats.^1,2

“We can only speculate about these sex-specific differences. However, future research would benefit from teasing out these differences and understanding them to lay a foundation for personalized approaches to retinal disease therapy,” Swaroop said in the release.

Swaroop and his research team are also developing additional and more potent reserpine-related drugs to be used as options to treat late-onset or slowly progressing IRDs. These drugs may also be able to stall vision loss in different types of aggressive retinitis pigmentosa until more effective treatments are developed that can reverse said vision loss.²

Although reserpine is no longer being used for treating high blood pressure due to its side effects, researchers hope that the low required dosage for treating retinal degeneration would quell said effects, according to the release.¹

Researchers note that the molecular target of reserpine in the retina remains unknown, while acknowledging the possibility for a different association in the retina. The reasons for biological sex bias in drug response must also be investigated, particularly whether retinas in female and male rats are predisposed differently to retinal pathology and interventions. “Overall, our findings highlight the broader application of small molecules derived from unbiased large-scale screening and underscore the importance of considering sex-specific differences in the development of treatments for IRDs,” the study authors stated.²

References:

1. Repurposing a blood pressure drug may prevent vision loss in inherited blinding diseases. News release. National Institutes of Health. April 15, 2025. Accessed May 6, 2025. https://www.nih.gov/news-events/news-releases/repurposing-blood-pressure-drug-may-prevent-vision-loss-inherited-blinding-diseases

2. Song HB, Campello L, Mondal AK, et al. Sex-specific attenuation of photoreceptor degeneration by reserpine in a rhodopsin P23H rat model of autosomal dominant retinitis pigmentosa. eLife. 2025. https://doi.org/10.7554/eLife.103888.1