The role of lymphocytes and phagocytes in age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is a leading cause of visual impairment of the elderly population. Since AMD is a multifactorial age-related disease with various genetic risk factors, the understanding of its complex pathophysiology is still limited. However, animal experiments, genome-wide association data and the molecular profiling of AMD patient samples have highlighted a key role of systemic and local immune processes that contribute to this chronic eye disease. In this overview article, we concentrate on the role of lymphocytes and mononuclear phagocytes and their interplay in triggering a persistent immune response in the AMD retina. We preferentially review findings from human immune cell analyses and complement these with related findings in experimental models. We conclude that both immune cell types as their signaling network may be a rich source to identify novel molecular targets for immunomodulation in AMD.

IFN-ß signaling dampens microglia reactivity but does not prevent from light-induced retinal degeneration.

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-ß) is a potent immune regulator, commonly used for the treatment of multiple sclerosis patients. We have previously shown that IFN-ß prevents microgliosis and choroidal neovascularization in a laser model of wet AMD. Here, we hypothesized that microglia modulation via IFN-ß 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-ß or vehicle every other day; starting at the day of exposure to 15,000 lux white light for 1 h. Systemic treatment with IFN-ß partially enhanced IFN-α/ß 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.