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

白内障仍然是全世界致盲的主要原因。氧化应激是暴露于B型紫外线辐射（UVR - B）引起的，目前被认为是导致人类和动物老年性白内障的主要因素之一。此外，已经确定的是，皮肤暴露于UVR-B不仅会导致晒黑和晒伤，还会通过神经肽信号调节局部和全身免疫，从而导致免疫抑制。最近有研究表明，单侧视网膜激光烧伤后，眼免疫特权也通过神经肽依赖途径在对侧眼发生改变。在之前的UVR-B辐射研究中，我们发现，作为一个意想不到的发现，只有一只眼睛暴露后，未经治疗的对侧眼睛的晶状体会失去透明度。我们假设已确定的神经肽P物质通过迄今未知的细胞和体液途径诱导我们在晶状体中观察到的对侧反应。右眼和左眼之间的眼部免疫串扰的识别和治疗方法的发展具有很高的临床意义。交感性眼炎是一种典型的自身免疫性疾病，单眼损伤会导致对侧正常眼出现威胁视力的炎症。为了验证我们的假设，C57Bl/6小鼠将被UVR-B单侧照射。我们将对白内障的发展进行量化和暴露，并分析对侧眼睛是否存在P物质。此外，我们将集中讨论治疗P物质介导的对侧眼病的治疗策略。这里的重点在于spantide I和II （P物质受体拮抗剂）可能阻断P物质信号通路，但更重要的是，我们将在体内模型中测试已被批准用于人类治疗并广泛用于临床实践的其他适应症的物质，如吲哚美辛、贝伐单抗和P物质受体拮抗剂阿瑞吡坦和奈妥吡坦。其优势在于，这些疗法有可能迅速应用于人类。因此，我们预计，眼睛之间神经肽信号通路的表征和可能的治疗方案的确定可以允许有希望的新策略来对抗许多眼病。

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.