Behnke Verena, Langmann Thomas
Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), 50931, Cologne, Germany.
Biochem Biophys Rep. 2020 Nov 26;24:100866. doi: 10.1016/j.bbrep.2020.100866. eCollection 2020 Dec.
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.
小胶质细胞的慢性激活与视网膜变性相关，这使得它们成为包括年龄相关性黄斑变性（AMD）在内的视网膜退行性疾病的潜在治疗靶点。干扰素-β（IFN-β）是一种有效的免疫调节剂，常用于治疗多发性硬化症患者。我们之前已经表明，在湿性AMD的激光模型中，IFN-β可预防小胶质细胞增生和脉络膜新生血管形成。在此，我们假设通过IFN-β调节小胶质细胞也可能抑制单核吞噬细胞反应性，从而在模拟干性AMD某些特征的光损伤模型中保护视网膜免受变性。BALB/cJ小鼠每隔一天腹腔注射10000 U IFN-β或赋形剂；从暴露于15000勒克斯白光1小时的当天开始。IFN-β的全身治疗部分增强了视网膜中的IFN-α/β受体（IFNAR）信号传导，并减少了视网膜下空间中重新激活的小胶质细胞数量。然而，光损伤四天后，未发现补体因子表达降低或视网膜厚度恢复。我们得出结论，IFNAR信号传导可调节视网膜小胶质细胞，但不能预防急性白光损伤引起的严重视网膜变性。
