NEUROIMMUNOMODULATION WITHIN THE EYE

眼内的神经免疫调节

• 批准号: 2391747
• 负责人: Andrew W Taylor
• 金额: $ 11.65万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2391747
• 关键词: T lymphocyte; calcitonin gene related peptide; denervation; enzyme linked immunosorbent assay; flow cytometry; inflammation; interferon gamma; interleukin 4; laboratory mouse; laboratory rabbit; leukocyte activation /transformation; melanocyte stimulating hormone; neuroimmunomodulation; passive immunization; polymerase chain reaction; somatostatin; transforming growth factors; tumor necrosis factor alpha; vasoactive intestinal peptide

The eye possesses a unique physiological adaptation that modifies the induction and expression of immunity within its tissues. This physiological adaptation is known as immune privilege. Normally the eye is an immune privileged site. The physiological role of immune privilege appears to be a mechanism by which the eye receives immune protection but avoids the destructive side-effects of immunogenic inflammation. Immunogenic inflammation associated with delayed hypersensitivity reactions can grossly distort the visual axis resulting in blindness. Consequently, immune protection within the eye involves a selective deficiency of T-cells that mediate delayed hypersensitivity. To control immunogenic inflammation, the cells and neurons within the ocular microenvironment produce immunomodulating factors that actively suppress T-cell inflammatory-mediating activities. Biochemical examination of aqueous human has revealed the identity of some of the immunomodulating factors. They are the neuropeptides alpha-melanocyte stimulating hormone (alpha- MSH), and vasoactive intestinal peptide (VIP), along with transforming growth factor-beta (TGF-beta). To demonstrate the activity of the neuropeptides with TGF-beta in the eye, the effects of normal aqueous humor. which contains the immunoregulatory cytokines produced in the eye, on effector T-cell activities will be examined. Primed T-cells treated with normal aqueous humor, neuropeptide depleted aqueous humor, or neuropeptides alone will be examined for the production of cytokines (secreted protein and mRNA expression) following antigen stimulation. The expectation is that when the neuropeptides are present in aqueous human T- cell inflammatory activity (production of IFN-gamma and TNFalpha) will be suppressed. To define the role of the neuropeptides in vivo, the inability of the eye to prevent immune-mediated inflammation will be examined in eyes that have been chemically denervated. The expectation is that such eyes can no longer prevent the induction of immune inflammation and therefore have lost an important part of ocular immune privilege. The results of this project will imply that immunomodulation in the eye involves a neurological component . Understanding thr activity of intraocular immunomodulatory factors will make it possible to manipulate the intraocular microenvironment in a manner that promotes immune elimination of pathogens and tumors without the binding consequence of immunogenic inflammation, to prevent or cure autoimmune ocular diseases, and to promote the success of ocular transplants of corneal and retinal cells and tissues.

眼睛具有独特的生理适应能力，可以改变 其组织内免疫的诱导和表达。 这 生理适应被称为免疫特权。 正常情况下眼睛是 免疫特权站点。 免疫特权的生理作用 似乎是眼睛获得免疫保护的一种机制，但是 避免免疫原性炎症的破坏性副作用。 与迟发型超敏反应相关的免疫原性炎症 会严重扭曲视轴，导致失明。 最后， 眼睛内的免疫保护涉及 T 细胞的选择性缺乏 介导迟发型超敏反应。 控制免疫原性 炎症、眼部微环境中的细胞和神经元 产生主动抑制 T 细胞的免疫调节因子 炎症介导活动。 水生化检查 人类已经揭示了一些免疫调节因子的身份。 它们是神经肽α-黑素细胞刺激激素（α- MSH）和血管活性肠肽（VIP），以及转化 生长因子-β（TGF-β）。 为了展示活动 眼睛中含有 TGF-β 的神经肽，正常房水的影响 幽默。其中含有眼睛产生的免疫调节细胞因子， 将检查效应 T 细胞活性。 处理过的引发 T 细胞 正常房水、神经肽耗尽房水，或 单独检查神经肽是否产生细胞因子 （分泌蛋白和 mRNA 表达）抗原刺激后。 这 预期的是，当神经肽存在于人 T- 水溶液中时， 细胞炎症活性（IFN-γ和TNFα的产生）将 压制。 为了定义神经肽在体内的作用，无法 将在眼睛中检查眼睛的结构，以防止免疫介导的炎症 已被化学去神经支配。 期待的是这样的眼睛 不能再阻止免疫炎症的诱导，因此 失去了眼部免疫特权的重要组成部分。 结果 该项目意味着眼睛的免疫调节涉及 神经系统成分。 了解眼内的活动 免疫调节因子将使操纵 以促进免疫消除的方式改善眼内微环境 病原体和肿瘤的结合，没有免疫原性的结合结果 炎症，预防或治疗自身免疫性眼部疾病，并促进 角膜和视网膜细胞和组织的眼部移植的成功。