Retinal Laser Burn Abolishes Ocular Immunity Privilege

描述（由申请人提供）：创伤后身体许多部位的免疫反应是炎症，随后是瘢痕形成和修复。在眼睛中，组织的炎症和疤痕会大大减少和模糊个体的视野。因此，眼睛已经进化成免疫特权区，从而抑制眼部炎症。为了研究免疫赦免，我们使用了一种称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）废除ACAID。这是令人感兴趣的，因为激光越来越多地用于治疗青光眼、近视和视网膜相关性黄斑变性。本提案的目的是了解RLB小鼠中导致ACAID丢失的机制。我们将使用以前的研究中的知识，详细说明免疫系统的组成部分（房水，F4/80+抗原呈递细胞和T调节细胞）对眼部免疫豁免的重要性。AIM 1将确定与WT小鼠相比，RLB小鼠中可能有助于诱导ACAID的能力的房水环境变化。AIM 2将确定RLB小鼠中缺乏免疫豁免是否是由于F4/80+ ARC缺陷所致。AIM 3将确定RLB后T细胞的特性。这项建议与公共卫生直接相关，因为它的发现可以导致治疗暴露于治疗性或意外激光照射的患者的改进策略。此外，了解激光治疗对视网膜的副作用将允许对患有糖尿病视网膜病变、葡萄膜炎和年龄相关性黄斑变性的患者进行更仔细和受控的治疗。总体而言，这些研究的结果可能会导致转化研究，检查因意外激光烧伤而接受治疗、在眼病治疗过程中接受RLB或出现眼外伤后的人类眼部环境（房水）的变化。或眼部手术。

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.