A retrospective study found that a commonly prescribed drug for Parkinson’s, L-DOPA, may delay or prevent AMD.
The authors previously found that a G protein–coupled receptor (GPR143) expressed in the retinal pigment epithelium binds to L-DOPA and downregulates vascular endothelial growth factor (VEGF). Because L-DOPA is made in pigmented tissues, and darker pigmentation is associated with a lower AMD risk, the researchers postulated that signaling through the L-DOPA receptor may underlie racial disparities in AMD incidence.
To test this theory, they combed through massive databases of medical chart data and analyzed 3 separate cohorts comprising of 17,000, 20,000 and 87 million (of which 15.2 million had ophthalmology records). They found that patients taking L-DOPA were significantly less likely to get dry AMD (OR=0.78, P<0.001), and when they did, its onset was significantly delayed (71 vs. 79, P<0.01). L-DOPA also significantly delayed the onset (75.8 vs 80.8, P<0.001) and the likelihood of developing wet AMD (OR 0.65, P<0.001).
Interestingly, the investigators also found that among patients with a history of both AMD and L-DOPA use, most received L-DOPA after an AMD diagnosis (76.9% and 70% from two different cohorts). This is against the expected trend as the mean age of L-DOPA prescription is 67, approximately 4 years before the average AMD age, further suggesting that L-DOPA is protective against AMD.
While the mechanism of L-DOPA on the pathophysiology of AMD is beyond the scope of this study, the authors propose that L-DOPA manipulates GPR143 signaling in the VEGF pathway to prevent AMD.
Dr. Paul A. Sieving, director of the National Eye Institute, a branch of the National Institutes of Health, said the research "suggests an intriguing link between patients taking L-DOPA and a lower incidence and delayed onset of AMD. Showing that L-DOPA causes this protective effect will require further investigation, but if confirmed it could lead to new drugs or combination therapies for AMD that target dopa-responsive cells in the retina."
The authors hope to launch a prospective clinical trial soon to further test the ability of this drug to prevent AMD.