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

单侧暴露于紫外线辐射后出现双侧白内障。

基本信息

批准号：
261319924
负责人：
Privatdozentin Dr. Linda Maren Meyer, Ph.D.
金额：
--
依托单位：
Universitäts-Augenklinik Bonn
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/261319924?language=en
关键词：
Bilateral cataract following unilateral exposure

项目摘要

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.

白内障仍然是世界范围内导致失明的主要原因。由紫外线B型辐射(UVR-B)引起的氧化应激，目前被认为是诱发人类和动物老年性白内障的主要因素之一。此外，众所周知，皮肤暴露于UVR-B不仅会导致皮肤晒黑和晒伤，还会通过神经肽信号调节局部和系统免疫，导致免疫抑制。最近的研究表明，单侧视网膜激光灼伤后，对侧眼的免疫豁免权也发生了改变，这是通过神经肽依赖的途径实现的。在之前的UVR-B辐射研究中，我们意外地发现，在只有一只眼睛暴露后，未经治疗的对侧眼睛也经历了晶状体透明度的丧失。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引起我们在晶状体中观察到的对侧反应。确定右眼和左眼之间的眼免疫串扰和开发治疗方法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，一种典型的自身免疫性疾病，一只眼睛的损伤会在正常的对侧眼睛引起威胁视力的炎症，这是一种类似的、迄今尚未解释的对侧眼球损伤后的对侧效应。为了验证我们的假设，C57BL/6小鼠将被单边照射UVR-B。白内障的发展将被量化和暴露，对侧眼将被分析P物质的存在。此外，我们将专注于治疗P物质介导的对侧眼病的治疗策略。这里的重点在于用Spantide I和II(物质受体拮抗剂)可能阻断P物质信号通路，但更重要的是，我们将在我们的体内模型中测试那些在人类治疗中被批准并广泛用于临床实践的物质，如消炎痛、贝伐单抗和P物质受体拮抗剂阿普利特和安非他明。优势可能是将这些疗法快速转移到人类环境中的可能性。因此，我们预计，眼睛之间神经肽信号通路的特征和可能的治疗方案的确定可能允许有希望的新策略来对抗多种眼部疾病。