Retinal Laser Burn Abolishes Ocular Immunity Privilege

描述(申请人提供)：创伤后身体许多部位的免疫反应是炎症，随后是疤痕和修复。在眼睛里，组织的炎症和疤痕会极大地减少和模糊个人的视野。因此，眼睛进化成了免疫特许区，从而抑制了眼部炎症。为了研究免疫豁免，我们使用了一种名为前房相关免疫偏离(ACAID)的实验模型。最近，我们发现视网膜激光烧伤(RLB)可以消除ACAID。这是因为激光越来越多地被用于治疗青光眼、近视和老年性黄斑变性。这项建议的目的是了解在RLB小鼠中导致ACAID丢失的机制。我们将利用以前研究中的知识，详细说明免疫系统的组成部分(房水、F4/80+抗原提呈细胞和T调节细胞)对眼睛免疫豁免很重要。目的1将确定房水环境的变化，这些变化可能有助于与WT小鼠相比，在RLB小鼠中诱导ACAID的能力。目的2将确定RLB小鼠缺乏免疫豁免是否是由于F4/80+ARC的缺陷所致。目的3将确定RLB后T细胞的特性。这项建议与公共健康直接相关，因为它的发现可以改进治疗暴露在治疗性或意外激光照射下的患者的策略。此外，了解激光治疗对视网膜的副作用将有助于更仔细和更有控制地治疗糖尿病视网膜病变、葡萄膜炎和年龄相关性黄斑变性患者。总体而言，这些研究的结果可能会导致进行转化性研究，以检查因意外激光烧伤而接受治疗、在眼部疾病治疗过程中接受RLB治疗或患有眼外伤或眼科手术的人的眼环境(房水)的变化。

DESCRIPTION (provided by applicant): The immune response in many areas of the body following trauma is inflammation followed by scarring and repair. In the eye, inflammation and scarring of tissues would greatly reduce and obscure the visual field of an individual. Therefore the eye has evolved into an immune privileged area, thereby inhibiting ocular inflammation. To study immune privilege we use an experimental model termed Anterior Chamber Associated Immune Deviation (ACAID). Recently, we have found that retinal laser burn (RLB) abolishes ACAID. This is of interest because lasers are gaining increase usage for treatment of glaucoma, myopia and Age-related macular degeneration. The purpose of this proposal is to understand the mechanism in RLB mice that lead to the loss of ACAID. We will use knowledge from previous studies that detail components (Aqueous humor, F4/80+ Antigen presenting cells and T-regulatory cells) of the immune system important for ocular immune privilege. AIM 1 will identify changes in the aqueous humor environment that might contribute to the ability to induce ACAID in RLB mice compared to WT mice. AIM 2 will determine if lack of immune privilege in the RLB mice is due to a defect in the F4/80+ ARC. AIM 3 will determine the characteristics of T cells after RLB. This proposal is directly relevant to public health because its findings can lead to improved strategies for treating patients exposed to therapeutic or accidental laser exposure. Moreover, understanding the side effects of laser treatment to the retina will allow for more careful and controlled treatment of patients with diabetic retinopathy, uveitis and age related macular degeneration. Overall, the results of the studies may lead to translational studies that examine the changes in the ocular environment (aqueous humor) of humans who are treated for accidental laser burn, receive RLB in the course treatment for their eye disease or present with post eye trauma or eye surgery.