Key Takeaways

• Retinal dopamine concentrations increased before structural degeneration was evident and remained elevated as inherited retinal degeneration progressed in 2 mouse models
• The findings demonstrate an association between retinal degeneration and altered dopamine and catecholamine signaling but do not establish whether increased dopamine is harmful, protective, or a consequence of disease
• Researchers are investigating the catecholamine system as a potential therapeutic target for mutation-independent treatment of inherited retinal degenerations

Researchers at the University of Eastern Finland (UEF) have identified early and persistent changes in the retinal dopamine system in mouse models of inherited retinal degeneration, findings that could help inform the development of treatments targeting disease mechanisms shared across different genetic forms of retinal disease.

The study, published in the Journal of Neurochemistry, examined the retinal dopamine system in mouse models representing 2 forms of inherited retinal degeneration. The investigators found that dopamine concentrations in retinal tissue increased before structural degeneration became apparent and remained elevated as disease progressed.¹

The researchers also identified alterations in dopamine metabolism and in the expression of genes associated with the broader catecholamine system compared with healthy retinas.

As part of the study, investigators measured and localized dopamine in the mouse retina using matrix-assisted laser desorption/ionization mass spectrometry imaging. According to UEF, this represents the first use of the technique to measure and localize retinal dopamine in mice. The work was conducted in collaboration with researchers at Uppsala University.

Dopamine is a catecholamine neurotransmitter with an important role in normal retinal development and function, although its role in retinal degeneration remains incompletely understood, according to researchers. Dopamine acts throughout the retina, with effects that vary among retinal cell types.

The findings suggest that the dopamine system is overactive during retinal degeneration, according to the investigators. However, the study did not establish whether increased dopamine contributes to degeneration, represents a protective response, or occurs as a consequence of other disease-related changes.

Inherited retinal degenerations encompass a genetically diverse group of disorders that progressively impair retinal function and can ultimately lead to blindness. Hundreds of genetic mutations have been implicated, complicating efforts to develop gene-specific treatments that can be applied broadly across the patient population.

A research group led by Henri Leinonen, associate professor at the UEF School of Pharmacy, is investigating a combination treatment targeting dopamine and the broader catecholamine system. The goal is to develop an approach that could potentially be used across forms of retinal degeneration regardless of the underlying genetic mutation.

The strategy builds on findings from animal studies in which compounds targeting the catecholamine system—including alpha-2 adrenergic agonists and dopamine D2 receptor agonists—have slowed retinal degeneration.

“We know that retinal degeneration can be slowed in animal models by targeting the catecholamine system. However, we do not know why,” Mr. Leinonen said. “The field is very fragmented: different laboratories have discovered promising individual compounds, but there is no unifying explanation for how they work. Our results are one piece of this puzzle.”

Mr. Leinonen added that continued investigation will be needed to determine the mechanism underlying these observations.

The researchers next plan to investigate the significance of elevated retinal dopamine during disease progression, including whether the increase accelerates degeneration, provides a protective effect, or is a secondary consequence of changes occurring in the degenerating retina.

Although those questions remain unresolved, the researchers noted that alterations in the catecholamine system occurred early and consistently in 2 genetically distinct disease models. The findings provide additional rationale for investigating the catecholamine system as a potential therapeutic target that could extend across multiple forms of inherited retinal degeneration.

Reference

1. Vainionpää K, Lappalainen E, Nilsson A, et al. Altered retinal dopamine homeostasis in murine models of retinitis pigmentosa. J Neurochem. 2026;170(9):e70552. doi:10.1111/jnc.70552