Mechanisms of intrinsic light responses in the ocular lens

我们通常认为神经视网膜是哺乳动物唯一对光有反应的组织。最近， 然而，已有研究表明，非典型视蛋白视蛋白3(OPN3，脑视蛋白)和视蛋白 5(OPN5，Neuropsin)在其他组织中表达。进一步调查这件事，Lang实验室已经 研究表明，OPN5在皮肤和大脑中调节光接收，而OPN3在脂肪中调节光接收 组织。在所有情况下，这些视蛋白调节非视网膜的直接、急性光反应。 组织。在这里，我们将人工晶状体识别为一种固有的光敏感组织。镜片 在培养中分离的人对蓝光(470 Nm)有强烈的反应，这会改变他们的光学特性 属性。根据初步数据，OPN3是生物体固有光响应所必需的 我们进一步证明，光刺激晶状体可以抑制细胞外信号转运蛋白的磷酸化 水通道蛋白0，蛋白激酶A底物，因为水通道蛋白0调节晶状体 透明度，我们假设依赖于OPN3的内在光反应调节 水通道蛋白通过cAMP-PKA途径的活性，从而影响晶状体的光学性能。 这一假说表明，晶状体有不同的光学状态，适应白天和 夜间视觉。为了更深入地了解这种独特的晶状体生物学，我们提出了三个 AIMS，(目标1)，确定OPN3使用哪种G蛋白在晶状体中发出信号，(Aim 2)，以 确认OPN3信号转导机制，以及该信号转导对水通道蛋白和 晶状体透明度，包括白内障形成和(目标3)，评估晶状体OPN3的影响 浅谈晶状体屈光力与眼屈光发育这个应用程序建立在悠久的历史之上 对晶状体感兴趣，并结合了晶状体细胞生物学方面的专业知识 史蒂夫·巴斯内特和拉斐尔·格里茨和马歇尔·帕杜的眼睛屈光发育。 人工晶状体中直接的、依赖于光和视素的光学变化的鉴定是 因此，当这项工作完成时，将从根本上改变我们的思维方式 作为感光器官的眼睛。也有可能这项工作将确定 晶状体作为近视治疗的新靶点。

We normally think of the neural retina as the only light-responsive tissue of mammals. Recently, however, it has been shown that the atypical opsins Opsin 3 (OPN3, encephalopsin) and Opsin 5 (OPN5, neuropsin) are expressed in other tissues. Investigating this further, the Lang lab has shown that OPN5 mediates light reception in skin and brain and that OPN3 does so in adipose tissue. In all cases, these opsins mediate direct, acute light responsiveness of the non-retinal tissue. Here we identify the ocular lens as an intrinsically light sensitive tissue. Lenses isolated in culture show an acute response to blue (470 nm) light that changes their optical properties. According to preliminary data, OPN3 is required for the intrinsic light response of the lens and we further show that light stimulation of the lens suppresses the phosphorylation of the water channel Aquaporin 0, a substrate of protein kinase A. Since Aquaporin 0 regulates lens transparency, we hypothesize that an OPN3-dependent, intrinsic light response regulates aquaporin activity via the cAMP-PKA pathway and thus the optical performance of the lens. This hypothesis implies that the lens has distinct optical states adapted to daytime and nighttime vision. Seeking a deeper understanding of this unique lens biology, we propose three aims, (Aim 1), To determine which G-protein OPN3 uses for signaling in the lens, (Aim 2), To confirm the OPN3 signaling mechanism, and the influence of that signaling on aquaporins and lens transparency including cataractogenesis, and (Aim 3), To assess the influence of lens OPN3 on lens refractive power and eye refractive development. This application builds on a long history of interest in the ocular lens from the Lang lab and combines expertise in lens cell biology from Steve Bassnett and eye refractive development from Rafael Grytz and Machelle Pardue. Identification of a direct, light- and opsin-dependent optical change in the ocular lens is unexpected and so when complete, this work will fundamentally change the way we think of the eye as a light sensing organ. There is also the possibility that this work will identify the lens as a new target for myopia treatment.