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IFN-β signaling dampens microglia reactivity but does not prevent from light-induced retinal degeneration
Verena Behnke1, Thomas Langmann1,2
1Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.
Abstract:
Chronic activation of microglia is associated with retinal degeneration, which makes them a potential therapeutic target for retinal degenerative diseases including age-related macular degeneration (AMD). Interferon-beta (IFN-β) is a potent immune regulator, commonly used for the treatment of multiple sclerosis patients. We have previously shown that IFN-β prevents microgliosis and choroidal neovascularization in a laser model of wet AMD. Here, we hypothesized that microglia modulation via IFN-β may also dampen mononuclear phagocyte reactivity and thereby protect from retinal degeneration in a light-damage paradigm mimicking some features of dry AMD. BALB/cJ mice received intraperitoneal injections of 10,000 U IFN-β or vehicle every other day; starting at the day of exposure to 15,000 lux white light for 1 h. Systemic treatment with IFN-β partially enhanced IFN-α/β receptor (IFNAR) signaling in the retina and reduced the number of reactivated microglia in the subretinal space. However, four days after light damage neither decreased expression of complement factors nor rescue of retinal thickness was found. We conclude that IFNAR signaling modulate retinal microglia but cannot prevent strong retinal degeneration as elicited by acute white light damage.
Insights
Interferon-beta (IFN-β) modulates retinal microglia but does not prevent degeneration in a light-induced damage model mimicking dry age-related macular degeneration (AMD). Further research is needed for effective AMD therapies.
Area of Science:
- Ophthalmology
- Neuroimmunology
- Retinal Degeneration
Background:
- Chronic microglial activation is linked to retinal degeneration, presenting microglia as a therapeutic target for diseases like age-related macular degeneration (AMD).
- Interferon-beta (IFN-β), an immune regulator used for multiple sclerosis, has previously shown potential in preventing microgliosis and choroidal neovascularization in wet AMD models.
Purpose of the Study:
- To investigate if microglia modulation by IFN-β can protect against retinal degeneration in a light-damage model simulating dry AMD.
- To assess the impact of systemic IFN-β treatment on mononuclear phagocyte reactivity and retinal integrity.
Main Methods:
- BALB/cJ mice were treated with IFN-β or vehicle and exposed to high-intensity white light.
- IFN-α/β receptor (IFNAR) signaling, microglial activation, complement factor expression, and retinal thickness were analyzed post-light damage.
Main Results:
- Systemic IFN-β treatment partially enhanced retinal IFNAR signaling and reduced subretinal microglia reactivation.
- However, IFN-β did not decrease complement factor expression or rescue retinal thickness four days after light damage.
Conclusions:
- IFNAR signaling modulation in retinal microglia is achievable with systemic IFN-β.
- IFN-β treatment alone is insufficient to prevent severe retinal degeneration induced by acute light damage in this model.
