Ageing is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown. Regulatory T cells were selectively depleted in both young (2–4 months) and aged (18–23 months) FoxP3-DTR mice. We evaluated neuroretinal degeneration, gliosis, subretinal space phagocyte infiltration, and retinal pigmented epithelium morphology through immunofluorescence analysis. Subsequently, aged Treg depleted animals underwent adoptive transfer of both young and aged regulatory T cells from wild-type mice, and the resulting impact on neurodegeneration was assessed. Statistical analyses employed included the U-Mann Whitney test, and for comparisons involving more than two groups, 1-way ANOVA analysis followed by Bonferroni’s post hoc test. Our study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes. Our findings demonstrate an essential role for regulatory T cells in maintaining age retinal homeostasis and preventing age-related neurodegeneration. This previously undescribed role of regulatory T cells in limiting retinal inflammation, RPE/choroid epithelium damage and subsequently photoreceptor loss with age, opens novel avenues to explore regulatory T cell neuroprotective and anti-inflammatory properties as potential therapeutic approaches for age-related retinal diseases.

中文翻译：

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调节性 T 细胞限制与年龄相关的视网膜炎症和神经退行性变

衰老是视网膜退行性疾病的主要危险因素，而视网膜退行性疾病是发达国家失明的最常见原因。这些病症包括与年龄相关的黄斑变性或糖尿病性视网膜病变。调节性 T 细胞通过限制健康和疾病中的炎症和组织损伤，在神经系统的免疫调节中发挥着至关重要的作用。由于视网膜长期以来被认为是免疫豁免部位，因此调节性 T 细胞在视网膜稳态和与年龄相关的视网膜疾病中的确切作用仍然未知。年轻（2-4 个月）和老年（18-23 个月）FoxP3-DTR 小鼠中的调节性 T 细胞均被选择性耗尽。我们通过免疫荧光分析评估了神经视网膜变性、神经胶质增生、视网膜下腔吞噬细胞浸润和视网膜色素上皮形态。随后，老年 Treg 耗尽的动物接受了来自野生型小鼠的年轻和老年调节性 T 细胞的过继转移，并评估了由此产生的对神经退行性变的影响。所采用的统计分析包括 U-Mann Whitney 检验，对于涉及两个以上组的比较，采用单向方差分析分析，然后进行 Bonferroni 事后检验。我们的研究表明，调节性 T 细胞的消除会导致年轻和老年小鼠的视网膜色素上皮细胞畸形和吞噬细胞在视网膜下腔积聚。然而，只有老年小鼠才会出现视网膜神经变性和神经胶质增生。令人惊讶的是，年轻而非衰老的调节性 T 细胞的过继转移逆转了这些变化。我们的研究结果表明，调节性 T 细胞在维持年龄视网膜稳态和预防与年龄相关的神经变性方面发挥着重要作用。调节性 T 细胞在限制视网膜炎症、RPE/脉络膜上皮损伤以及随后随年龄增长的光感受器丧失方面的这种先前未被描述的作用，为探索调节性 T 细胞的神经保护和抗炎特性作为与年龄相关的视网膜疾病的潜在治疗方法开辟了新的途径。