分泌性IgM缺乏改变视网膜景观,增强与衰老相关的神经变性。

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Sarah E Webster, Sydney M Les, Nico Deleon, Daken M Heck, Naomi L Tsuj, Michael J Clemente, Prentiss Jones, Nichol E Holodick
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引用次数: 0

摘要

背景:视网膜作为中枢神经系统的一部分,以及眼内其他结构的维护对于视力的保护至关重要。衰老增加了视力损害的患病率,包括青光眼、黄斑变性和糖尿病视网膜病变。视网膜主要由神经胶质细胞维持;然而,最近的文献表明淋巴细胞可能在中枢神经系统组织的稳态中发挥作用。天然抗体由B细胞产生,无需感染或免疫,维持组织稳态。在这里,我们探讨了B淋巴细胞产生的天然免疫球蛋白M (IgM)在小鼠衰老过程中维持视网膜健康的潜在作用。结果:我们的研究结果表明,小鼠和人的玻璃体中都含有IgM和IgG,提示这些免疫球蛋白可能在眼功能中起作用。此外,我们观察到缺乏分泌IgM(µs-/-)的老年小鼠表现出明显的视网膜变性,伴有反应性胶质细胞增生和促炎细胞因子环境。这与衰老的野生型形成对比,后者保留了分泌IgM的能力,并维持了更好的视网膜结构和抗炎环境。除了这些发现之外,分泌IgM的缺失与视网膜色素上皮的显著改变有关,包括其形态的破坏和应激增加的迹象。这在血液-视网膜屏障的变化中进一步观察到,这对视网膜稳态的调节至关重要。结论:这些数据表明,缺乏分泌的IgM与视网膜微环境的改变之间存在一种以前未被认识到的关联,从而导致衰老过程中视网膜变性的加剧。虽然确切的机制尚不清楚,但这些发现强调了分泌IgM在长期支持视网膜健康的过程中的潜在重要性。通过增加我们对眼老化的理解,这些结果表明免疫系统在老年视网膜功能和完整性中具有更广泛的作用,为探索年龄相关视网膜疾病的免疫相关干预开辟了新的领域。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Secreted IgM deficiency alters the retinal landscape enhancing neurodegeneration associated with aging.

Background: Maintenance of the retina, part of the central nervous system, and other structures in the eye is critical for vision preservation. Aging increases the prevalence of vision impairment, including glaucoma, macular degeneration, and diabetic retinopathy. The retina is primarily maintained by glial cells; however, recent literature suggests that lymphocytes may play a role in the homeostasis of central nervous system tissues. Natural antibodies are produced by B cells without infection or immunization and maintain tissue homeostasis. Here, we explored the potential role of natural immunoglobulin M (IgM) produced by B lymphocytes in maintaining retinal health during aging in mice.

Results: Our results indicate that the vitreous humor of both mice and humans contains IgM and IgG, suggesting that these immunoglobulins may play a role in ocular function. Furthermore, we observed that aged mice lacking secreted IgM (µs-/-) exhibited pronounced retinal degeneration, accompanied by reactive gliosis, and a proinflammatory cytokine environment. This contrasts with the aged wild-type counterparts, which retain their ability to secrete IgM and maintain a better retinal structure and anti-inflammatory environment. In addition to these findings, the absence of secreted IgM was associated with significant alterations in the retinal pigment epithelium, including disruptions to its morphology and signs of increased stress. This was further observed in changes to the blood-retinal-barrier, which is critical for regulation of retinal homeostasis.

Conclusions: These data suggest a previously unrecognized association between a lack of secreted IgM and alterations in the retinal microenvironment, leading to enhanced retinal degeneration during aging. Although the precise mechanism remains unclear, these findings highlight the potential importance of secreted IgM in processes that support retinal health over time. By increasing our understanding of ocular aging, these results show that there is a broader role for the immune system in retinal function and integrity in advanced age, opening new areas for the exploration of immune-related interventions in age-associated retinal conditions.

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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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