Age-related macular degeneration (AMD) is a prevalent eye condition among the elderly. It is caused by inflammation of the macula, which is the region of the eye that regulates crisp, straight-ahead vision.AMD is now the most frequent cause of visual loss in persons over the age of 50 all over the world.
A new study conducted by Meenakshi Ambati and team showed that patients with depression who were treated with fluoxetine had a lower risk of acquiring dry AMD. These data, taken together, point to fluoxetine as a possible drug-repurposing candidate for dry AMD.
The findings of this study were published in Proceedings of the National Academy of Sciences of the United States of America.
Dry AMD causes vision loss due to deterioration of the retinal pigmented epithelium (RPE). The accumulation of Alu RNAs, which are noncoding transcripts of a human retrotransposon, contributes to RPE cell death. By activating the NLRP3-ASC inflammasome, Alu RNA causes RPE degeneration. Researchers investigated the possibility of repurposing medications previously licensed for other illnesses to treat dry AMD.
An investigational medication known as CY-09 has been discovered to inhibit the inflammatory process that causes dry AMD by attaching to a protein known as NLRP3. The testing procedure necessary to approve a new medicine, on the other hand, might take years or decades. The researchers sought medications that are structurally and functionally comparable to CY-09 that are currently approved by the US Food and Drug Administration (FDA). For more than three decades, fluoxetine has been routinely used to treat depression. The researchers examined health claims data from more than 100 million Americans gathered between 2006 and 2018 to investigate if the medicine may reduce the incidence of dry AMD in persons.
Observations made in this study:
1. The researchers discovered that fluoxetine—an antidepressant best known by its trademark name, Prozac—was structurally identical to CY-09. Further research in the lab discovered that fluoxetine, like CY-09, may bind to NLRP3.
2. In cell tests, fluoxetine inhibited the inflammatory cascade initiated by NLRP3 that finally leads to eye injury. Fluoxetine injections into the eye protected the macula against inflammation and degeneration in a mouse model of dry AMD. Eight other antidepressants, on the other hand, did not slow the course of AMD.
3. After controlling for other characteristics known to be linked with dry AMD, such as age, gender, smoking, BMI, and general health, the researchers discovered that those who used fluoxetine at some point in their life had a 15% decreased chance of getting dry AMD.
In conclusion, these discoveries are an intriguing illustration of the potential of drug repurposing, which involves reusing current medications in novel and unexpected ways. Finally, the best method to see if fluoxetine helps macular degeneration is to conduct a prospective clinical study.
Reference:
Ambati, M., Apicella, I., Wang, S., Narendran, S., Leung, H., Pereira, F., Nagasaka, Y., Huang, P., Varshney, A., Baker, K. L., Marion, K. M., Shadmehr, M., Stains, C. I., Werner, B. C., Sadda, S. R., Taylor, E. W., Sutton, S. S., Magagnoli, J., & Gelfand, B. D. (2021). Identification of fluoxetine as a direct NLRP3 inhibitor to treat atrophic macular degeneration. In Proceedings of the National Academy of Sciences (Vol. 118, Issue 41, p. e2102975118). Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2102975118