NEUROIMMUNOMODULATION WITHIN THE EYE

眼睛具有独特的生理适应性， 在其组织内诱导和表达免疫。 这 生理适应被称为免疫豁免。 通常眼睛是 一个免疫特权区 免疫豁免的生理作用 似乎是眼睛接受免疫保护的机制， 避免了免疫原性炎症的破坏性副作用。 与迟发性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，委员会认为， 眼内的免疫保护涉及T细胞的选择性缺乏 介导迟发型超敏反应 为了控制免疫原性 炎症，眼内微环境中的细胞和神经元 产生免疫调节因子，积极抑制T细胞 炎症介导的活动。 房水生化检查 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- 血管活性肠肽（VIP），沿着转化 生长因子-β（TGF-β）。 为了证明 神经肽与TGF-β在眼睛，正常的影响， 幽默其含有眼内产生的免疫调节细胞因子， 对效应T细胞活性的影响。 经处理的致敏T细胞 具有正常的房水，神经肽耗尽的房水，或 将单独检查神经肽的细胞因子产生 （分泌的蛋白质和mRNA表达）。 的 预期是，当神经肽存在于水性人T- 细胞炎症活性（IFN-γ和TNF α的产生）将被抑制。 抑制 为了确定神经肽在体内的作用， 预防免疫介导的炎症将在眼睛中进行检查 已经被化学方法切除了神经。 人们期望这样的眼睛 不能再阻止免疫炎症的诱导， 已经失去了眼部免疫豁免的重要组成部分。 的结果 这个项目将意味着眼睛中的免疫调节涉及一种 神经系统成分。 对眼内Thr活性的认识 免疫调节因子将使操纵 眼内微环境以促进免疫消除的方式 没有免疫原性的约束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 角膜和视网膜细胞和组织的眼部移植的成功。

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.