Parkinson's Can Show Up in Your Eyes Before It Affects Your Body

Parkinson’s disease, in addition to causing tremors and muscle stiffness, can also affect vision from its early stages. A simple test called electroretinography (ERG), which assesses the retina’s response to light, can identify these early visual changes. This study showed that both mice and people with recent Parkinson’s, especially women, have clear signs of retinal dysfunction. These findings indicate that ERG can help in the early diagnosis and monitoring of the disease.

Parkinson’s disease (PD) is a progressive neurological disorder, best known for its effects on movement, such as tremors, muscle stiffness and slowness of movement. These symptoms occur because there is a gradual loss of neurons that produce dopamine, a neurotransmitter essential for motor control, in a specific area of ​​the brain called the substantia nigra. This neuronal degeneration is associated with toxic forms of the protein α-synuclein (aSyn).

But Parkinson's doesn't just affect the body: it also causes a range of other problems, such as depression, sleep disorders, memory difficulties and even changes in the functioning of the autonomic nervous system, which controls automatic functions such as breathing or heartbeat.

Some of these symptoms, such as loss of smell and sleep problems, can even appear years before motor symptoms.

In recent years, researchers have begun to investigate other early signs of Parkinson's disease, and the eyes have become a particular focus of attention. This is because the retina, which is the part of the eye responsible for capturing light and transmitting visual signals to the brain, also appears to undergo changes in people with Parkinson's.

Problems such as difficulty seeing contrasts, perceiving colors or processing images can be linked to defects in the cells of the retina. One of the most effective ways to detect these changes is through electroretinography (ERG), a simple and painless test that measures how the retina reacts to light. It works like an “electrocardiogram for the eye”, revealing whether the cells of the retina are functioning well or not.

Electroretinography generates different waveforms, each associated with a type of cell or visual process. For example, the “a wave” indicates the response of the photoreceptors (which capture the light), while the “b wave” shows the activity of the bipolar cells, which transmit this information further.

There are also specific responses for the ganglion cells, which are the last to process the signals before sending them to the brain. In people with Parkinson's, several of these waves appear weakened or delayed, suggesting that the retina also suffers from the disease.

A) Positioning of the device for eye recordings using electroretinography (ERG). B) Example of ERG responses to standard light-adapted flash stimuli. C) Device screen showing the ERG recording setup, with the eye visible and the pupil detected (highlighted by the blue circle). D) Responses to standard light-adapted 30 Hz flicker stimulus. Copyright © 2023 Omar A. Mahroo

The study we are discussing was done in both mice genetically modified to mimic Parkinson's disease and in humans diagnosed early in the disease. The mean age was 63 years, the disease duration was 4 years, a total of 12 males and 8 females, and healthy controls matched by mean age of 61 years, 9 males and 11 females.

The researchers found that, already in the early stages, the mice showed alterations in the functioning of the retina, mainly in females. The waves from the electroretinography exam showed less activity in cells responsible for processing light and sending visual signals to the brain.

This image shows a portion of the eye (the retina) of mice analyzed with a special fluorescence technique to highlight different cells. The blue areas indicate the cell nuclei, the white shows a specific type of retinal cell that expresses Calbindin, and the cyan (a shade of light blue) reveals a change in the protein alpha-synuclein, a hallmark of Parkinson's disease. This change was seen only in mice with a genetic model of Parkinson's disease (M83 ho), and not in healthy mice (B6). These changes appear in an area of ​​the retina responsible for processing light, suggesting that signs of the disease may begin to affect the eye even before classic motor symptoms appear. GCL (ganglion cell layer), IPL (inner plexiform layer), INL (inner nuclear layer), OPL (outer plexiform layer), ONL (outer nuclear layer).

These changes were confirmed by analysis of retinal tissue, which showed clear signs of the abnormal protein α-synuclein, a major cause of damage in Parkinson's.

The same pattern was observed in humans recently diagnosed with the disease: women showed similar changes in retinal responses, with weaker signals coming from bipolar, ganglion and amacrine cells (a type of cell that helps regulate visual signals). This suggests that these tests may serve as early markers, that is, detectable signs that indicate the onset of the disease even before the more well-known symptoms appear.

In summary, the study indicates that changes in the retina, detected by a simple and accessible test such as electroretinography, may become a useful tool for the early diagnosis of Parkinson's disease, especially in women. This opens up new possibilities for monitoring the progression of the disease and starting treatments earlier, which can significantly improve the quality of life of patients.

READ MORE:

Early detection of Parkinson’s disease: Retinal functional impairments as potential biomarkers

Victoria Soto Linan, Véronique Rioux, Modesto Peralta, Nicolas Dupré, Marc Hébert and Martin Lévesque

Neurobiology of Disease. Volume 208, May 2025, 106872DOI: 10.1016/j.nbd.2025.106872

Abstract:

Parkinson's disease is typically diagnosed after substantial neurodegeneration despite early non-motor symptoms manifesting decades earlier. These changes offer a promising avenue for diagnostic exploration, especially within the eye, which has been proposed as a “window to the brain.” The aim was to identify biomarkers by validating the use of electroretinography, a non-invasive technique, to detect early retinal function anomalies reflecting central dysfunction. Homozygous M83 transgenic mice (n = 10 males, 11 females), overexpressing human A53T α-synuclein, underwent behavioral tests and electroretinography measurements. Histological evaluation was performed at four months to analyze synucleinopathies and neurodegeneration. Electroretinography was also conducted with idiopathic PD patients (mean age 63.35 ± 7.73; disease duration 4.15 ± 2.06; H&Y score 2.07 ± 0.59; n = 12 males, 8 females) and healthy age-matched controls (mean age 61.65 ± 8.39; n = 9 males, 11 females). Rodent electroretinography revealed reduced photopic b-wave, PhNR b-wave, and PhNR-wave amplitudes at two and four months, particularly in females, indicating bipolar and retinal ganglion cell impairment. Based on retinal histological assessment, these changes might arise from α-synuclein pathology occurring in outer retinal layers. Likewise, the scotopic b-wave and PhNR waveform were similarly impaired in female participants with Parkinson's disease. The scotopic oscillatory potentials isolated further identified an attenuated amacrine cell output in females. Findings from both mice and human cohorts indicate that retinal functional impairments can be detected early in the progression of Parkinson's disease, particularly among females. These tools show promise in facilitating early diagnosis, disease monitoring, therapeutic intervention, and ultimately enhancing patient outcomes.