NEUROIMMUNOMODULATION WITHIN THE EYE

眼睛拥有一种独特的生理适应能力，这种适应能力可以改变 在其组织内诱导和表达免疫。这 生理适应被称为免疫豁免。正常情况下，眼睛是 一个免疫特权网站。免疫豁免权的生理作用 似乎是眼睛获得免疫保护的一种机制，但 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。因此， 眼睛内的免疫保护涉及T细胞的选择性缺陷 调节迟发性超敏反应的物质。控制免疫原性 炎症、眼部微环境内的细胞和神经元 产生主动抑制T细胞的免疫调节因子 炎症调节活动。房水生化检验 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-黑素细胞刺激素(α-黑素细胞刺激素)。 MSH)、血管活性肠肽(VIP)以及转化 生长因子-β(TGF-β)。以演示 神经肽与转化生长因子-β在眼内正常房水中的作用 幽默感。它含有眼睛中产生的免疫调节细胞因子， 对效应器T细胞的活性进行检测。治疗过的预激T细胞 房水正常，神经肽耗尽房水，或 只有神经肽才能检测细胞因子的产生。 (分泌蛋白和信使核糖核酸的表达)。这个 预期是，当神经肽存在于人T-水溶液中时- 细胞炎症活动(产生干扰素-γ和肿瘤坏死因子α)将是 被压制了。为了确定神经肽在体内的作用，不能 预防免疫介导的炎症的眼睛将在眼睛中进行检查 它们已经失去了化学上的神经。人们的期望是，这样的眼睛 不再能防止免疫炎症的诱导，因此 已经失去了眼睛免疫特免权的一个重要部分。结果是 这个项目将意味着眼睛中的免疫调节涉及一种 神经部分。对眼内活动的认识 免疫调节因子将使我们有可能操纵 眼内微环境促进免疫消除 没有免疫原性的约束性后果的病原体和肿瘤 炎症，预防或治疗自身免疫性眼病，并促进 成功的角膜和视网膜细胞和组织眼移植。

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.