Parkinson's treatment could delay progression of one form of AMD
Age-related macular degeneration (AMD) is the leading cause of visual impairment in people over 50. Improving treatment options for patients is a major challenge for research. In a new study, a team of researchers from Inserm, CNRS and Sorbonne University at the Institut de la Vision[1] in Paris, describe the efficacy of dopaminergic drugs in slowing the progression of one form of the disease, the neovascular or "wet" form characterized by the proliferation of dysfunctional blood vessels under the retina. These specific drugs are already used in the treatment of Parkinson's disease. These results are published in The Journal of Clinical Investigation.
Understanding AMD
AMD is a multifactorial retinal disease that affects people over 50. It corresponds to a deterioration of part of the retina - the macula - and can lead to the loss of central vision. Although highly incapacitating, it never leads to total blindness, since the peripheral part of the retina remains intact.
There are two forms of the disease with roughly equivalent prevalence: the neovascular, or "exudative" or "wet" form, and the atrophic, or "advanced dry" form (see box).
While there is currently no cure for the dry form of the disease, the neovascular form can be slowed by regular injections administered directly into the patient's eye (so-called "intravitreal" injections).
Although necessary, these injections can represent a significant therapeutic burden, given the frequency of injections (monthly or bimonthly), depending on the progression of the disease. It is therefore worth continuing to identify new alternatives for patients.
Medicines for Parkinson's
Previous epidemiological studies have already highlighted a possible association between Parkinson's disease and a reduced risk of neovascular AMD[2]. In a new study, researchers from Inserm, CNRS and Sorbonne University's Institut de la Vision have explored the underlying mechanisms that might explain this potential protection.
In cellular and animal models, scientists have shown that L-Dopa, a dopaminergic[3] drug used to treat Parkinson's disease, activates a specific brain receptor called DRD2. This activation of DRD2 blocks the formation of new blood vessels in the eye, a key process in the development of neovascular AMD.
To investigate further, the team then analyzed the health data of over 200,000 neovascular AMD patients in France[4].
They showed that patients who took L-Dopa or other DRD2 receptor-inhibiting drugs (DRD2 agonists) to treat their Parkinson's disease developed neovascular AMD later in life, and required fewer intravitreal injections.
In fact, patients treated with these drugs for their Parkinson's disease reported the disease at 83 years of age, compared with 79 for other patients.
"These results open up unprecedented prospects for patients suffering from wet AMD. We now have a serious lead for delaying the progression of this disease and reducing the burden of current treatments", explains Florian Sennlaub, Inserm Research Director at the Institut de la Vision (CNRS/Sorbonne University/Inserm).
Thibaud Mathis, university professor and hospital practitioner in the ophthalmology department of the Croix-Rousse Hospital - Hospices civils de Lyon, and researcher at Lyon 1 University and the Institut de la vision, agrees:
"These results suggest that dopaminergic drugs, beyond their role in Parkinson's disease, may have a beneficial effect in the prevention and treatment of neovascular AMD."
Although further clinical studies will be needed to confirm these results and assess the efficacy and safety of these drugs in the treatment of AMD, this discovery opens up encouraging new prospects for the fight against the neovascular form, offering the hope of a more effective and less burdensome treatment for patients.
Different forms of AMD
Wet AMD is characterized by the proliferation of new, dysfunctional vessels beneath the retina. Blood can diffuse through their walls, leading to the formation of macular edema. Occasionally, blood leaks from these vessels, leading to retinal haemorrhages. Wet AMD progresses rapidly if left untreated. In the past, central vision loss could appear in a matter of weeks or even days. Today, this process can be halted with drugs (anti-VEGF) injected into the eye, which inhibit the growth of new vessels. Nevertheless, after several years of treatment, the disease can evolve into an atrophic form.
In atrophic or "advanced dry" AMD, the photoreceptors in the macula gradually disappear, followed by the cells of the retinal pigment epithelium. This process generates holes of increasing size in the macula, visible by simple observation of the retina (fundus). This is a slow process, and it usually takes between five and ten years before the patient loses central vision. Currently, no treatment for this form of AMD is authorized in Europe.
Mixed forms of the disease can also be observed, and each of these two forms can precede the onset of the second.
[1]This work is the result of a collaboration with teams from the University and University Hospital of Lyon, the University of Burgundy and the Brain Institute in Paris.
[2]Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration, Max J Hyman et al. Ophthalmology retina 2023
[3]Dopaminergic drugs provide the dopamine necessary for brain function. In Parkinson's disease, dopamine reduces the intensity of tremors, rigidity and akinesia.
[4] Data from the French National Health Data System (SNDS).