Bilateral cataract following unilateral exposure to ultraviolet radiation. Ocular immune cross-talk and immunmodulation between left and right eye.

白内障仍然是世界范围内导致失明的主要原因。由暴露于紫外线辐射类型B（UVR - B）引起的氧化应激是当今认为的诱发人类和动物年龄相关性白内障的主要因素之一。此外，已经确定皮肤暴露于UVR-B不仅诱导晒黑和晒伤，而且还调节局部和全身免疫，从而通过神经肽信号传导导致免疫抑制。最近研究表明，单侧视网膜激光烧伤后，对侧眼的眼免疫赦免也通过神经肽依赖性途径发生改变。在先前的UVR-B辐射研究中，我们发现，作为意外的发现，在仅一只眼睛暴露后，未处理的对侧眼睛也经历透镜的透明度损失。我们推测，已鉴定的神经肽P物质通过迄今未知的细胞和体液途径诱导我们在透镜中观察到的对侧反应。右眼和左眼之间的眼部免疫串扰的鉴定和疗法的开发具有高度的临床相关性。一只眼睛受损后出现的对侧效应类似，但迄今无法解释。交感性眼炎是一种典型的自身免疫性疾病，其中一只眼睛受损会导致对侧正常眼睛出现威胁视力的炎症。为了检验我们的假设，C57 B1/6小鼠将单侧照射UVR-B。白内障的发展将被量化和曝光，以及对侧的眼睛将被分析P物质的存在。此外，我们将集中在治疗策略，以治疗P物质介导的对侧眼病。本文的重点在于Spantide I和II（P物质受体拮抗剂）对P物质信号传导途径的可能阻断，但更重要的是，我们将在体内模型中测试已批准用于人类治疗并广泛用于其他适应症的临床实践的物质，如吲哚美辛、贝伐单抗和P物质受体拮抗剂阿瑞匹坦和奈妥匹坦。优势可能是这些疗法快速转移到人类情况的可能性。因此，我们预计，眼睛之间的神经肽信号通路的表征和可能的治疗方案的识别可以允许有希望的新策略来对抗许多眼科疾病。

Cataract still is the leading cause of blindness worldwide. Oxidative stress, as provoked from exposure to ultraviolet radiation type B (UVR - B), is today held one of the main factors inducing age-related cataract in humans and animals. Furthermore it is well established that exposure of the skin to UVR-B induces not only tanning and sunburn but also modulates local and systemic immunity leading to immunosuppression via neuropeptide signaling. Recently it has been shown that the ocular immune privilege is altered also in the contralateral eye following unilateral retinal laser burn via a neuropeptide dependent pathway. In previous UVR-B- irradiation studies we found, as an unexpected finding, that after exposure of only one eye also the untreated, contralateral eye undergoes a loss of transparency in the lens. We postulate that the identified neuropeptide substance P via so far unknown cellular and humoral pathways induces the contralateral reaction we observed in the lens. The identification of an ocular immune cross talk between right and left eye and the development of therapies is of high clinical relevance. A similar, so far unexplained contralateral effect after damage to one eye occurs in sympathetic ophthalmitis, a prototypical autoimmune disease in which injury to one eye causes sight-threatening inflammation in the otherwise normal contralateral eye. To test our hypothesis, C57Bl/6 mice will be irradiated unilaterally with UVR-B. Cataract development will be quantified and exposed as well as contralateral eyes will be analyzed for presence of substance P. Furthermore we will concentrate on therapeutic strategies to treat substance P mediated contralateral eye disease. Here the focus lies on possible blocking of substance P signaling pathways with spantide I and II (substance P receptor antagonist) but more importantly we will test substances in our in vivo model that are approved in human therapy and widely used in clinical practice for other indications such as indomethacin, bevacizumab and the substance P receptor antagonists aprepitant and netupitant. Of advantage could be the possibility of a fast transfer of these therapies to the human situation. Thus we anticipate that the characterization of neuropeptide signaling pathways between the eyes and the identification of possible treatment options could allow for promising new strategies to fight numerous eye diseases.