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人的视野。因此，眼睛已经进化成一个免疫特权区域，从而抑制眼部炎症。为了研究免疫特权，我们使用了前房相关免疫偏差（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。这是有趣的，因为激光越来越多地用于治疗青光眼、近视和老年性黄斑变性。本提案的目的是了解RLB小鼠导致ACAID丧失的机制。我们将利用先前研究的知识，详细介绍免疫系统中对眼部免疫特权重要的成分（房水、F4/80+抗原提呈细胞和t调节细胞）。AIM 1将确定与WT小鼠相比，RLB小鼠房水环境的变化可能有助于诱导ACAID的能力。AIM 2将确定RLB小鼠缺乏免疫特权是否是由于F4/80+ ARC缺陷所致。AIM 3测定RLB后T细胞的特征。这一建议与公共卫生直接相关，因为其研究结果可以改善治疗暴露于治疗性或意外激光照射的患者的策略。此外，了解激光治疗对视网膜的副作用将使糖尿病视网膜病变、葡萄膜炎和年龄相关性黄斑变性患者的治疗更加谨慎和可控。总的来说，这些研究的结果可能导致转译性研究，以检查因意外激光烧伤而接受治疗的人，在眼病治疗过程中接受RLB的人，或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.