Central Regulation of the Peripheral Visual System

周边视觉系统的中央调节

• 批准号: 7126166
• 负责人: Robert Nelson Jinks
• 金额: $ 18.73万
• 依托单位: FRANKLIN AND MARSHALL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126166
• 关键词: arrestins; eye; lighting; model; myosins; proteins; retina

DESCRIPTION (provided by applicant): Everyday, the light-sensitive cells in our retinas, our photoreceptors, shed and renew a portion of their light-sensitive membrane. Why this process occurs is not completely understood, however; it is essential for healthy vision in humans and animals. In fact, retinal degeneration occurs in mutant rats unable to shed their photosensitive membrane. In most animals, shedding of the photosensitive membrane is regulated by a biological clock (circadian rhythm) and triggered by that clock and/or by light. Relatively little is known, however, about how the biological clock and light interact to trigger and regulate daily shedding and renewal of photosensitive membrane. The lateral eye of the horseshoe crab (Limulus) has long served as an important system for the study of photoreceptor membrane shedding and renewal. Its photoreceptors are similar in many important ways to human rod photoreceptors. In the currently funded project (R15 EY13196), we developed and tested a model for the interaction of light and the biological clock in the regulation of daily transient photosensitive membrane shedding. To date, we have learned that the clock primes the retina for transient shedding and renewal through cAMP-dependent protein kinase (PKA) stimulated downregulation of photoreceptor protein synthesis. This competing continuation application proposes to continue to evaluate our model through the following two specific aims: (1). Investigate whether downregulation of visual arrestin expression is required to prime the lateral eye for transient rhabdom shedding (TRS), and whether the actin-binding protein myosin III is required to stabilize the rhabdom against TRS during post-dawn daylight. (2). Determine whether PKA acts through, or in competition with, a MAP kinase pathway to decrease photoreceptor protein synthesis during octopaminergic priming of the lateral eye for TRS. The P.I. and his undergraduate student collaborators will use gene silencing through the RNA interference pathway to knockdown the expression of proteins (arrestin and myosin III). Our model hypothesizes that the clock regulates the expression of these proteins, and possibly others, to maintain healthy vision through proper regulation of daily turnover of the photosensitive membrane. Public Health Significance - The use of a simple invertebrate retina with many similarities to the human retina is critical to the development of translational models that can be used to drive research to prevent retinal degeneration and blindness caused by failures in daily photoreceptor outer segment turnover. Involving undergraduate students in biomedical research is critical to this Nation's ability advance our public health through recruitment of our brightest young citizens into medicine and biomedical research, and to produce new generations of well-informed science teachers and College professors to inform the Citizenry.

描述（由申请人提供）：每天，我们视网膜中的光敏细胞，我们的光感受器，脱落和更新一部分光敏膜。然而，这个过程发生的原因尚不完全清楚；它对人类和动物的健康视力至关重要。事实上，视网膜变性发生在无法脱落光敏膜的突变大鼠身上。在大多数动物中，光敏膜的脱落是由生物钟（昼夜节律）调节的，并由生物钟和/或光触发。然而，对于生物钟和光如何相互作用来触发和调节光敏膜的日常脱落和更新，人们知之甚少。马蹄蟹（鲎）的侧眼一直是研究光感受器膜脱落和更新的重要系统。它的光感受器在许多重要方面与人类的杆状光感受器相似。在目前资助的项目（R15 EY13196）中，我们开发并测试了光和生物钟在调节每日瞬态光敏膜脱落中的相互作用模型。到目前为止，我们已经了解到，生物钟通过camp依赖性蛋白激酶（PKA）刺激光感受器蛋白合成的下调，为视网膜的短暂脱落和更新提供了条件。这个竞争性的延续应用程序建议通过以下两个具体目标继续评估我们的模型：(1)。研究是否需要下调视觉抑制蛋白的表达来为侧眼的瞬时横纹肌脱落（TRS）做准备，以及是否需要肌动蛋白结合蛋白肌球蛋白III来稳定横纹肌在黎明后的白天抵抗TRS。（2）. 确定PKA是否通过MAP激酶途径，或与MAP激酶途径竞争，在TRS的侧眼八爪胺能启动过程中减少光感受器蛋白的合成。P.I.和他的本科生合作者将通过RNA干扰途径使用基因沉默来抑制蛋白质（阻滞蛋白和肌球蛋白III）的表达。我们的模型假设生物钟调节这些蛋白的表达，可能还有其他蛋白，通过适当调节感光膜的日常更新来维持健康的视力。公共卫生意义-使用与人类视网膜有许多相似之处的简单无脊椎动物视网膜对于开发翻译模型至关重要，该模型可用于推动研究，以防止因日常光感受器外段转换失败而导致的视网膜变性和失明。让本科生参与生物医学研究，对于我们国家通过招募最聪明的年轻公民从事医学和生物医学研究来促进我们的公共卫生，以及培养新一代知识渊博的科学教师和大学教授来为公民提供信息，至关重要。

项目成果

Central regulation of photosensitive membrane turnover in the lateral eye of Limulus, II: octopamine acts via adenylate cyclase/cAMP-dependent protein kinase to prime the retina for transient rhabdom shedding.

鲎 II 侧眼光敏膜周转的中枢调节：章鱼胺通过腺苷酸环化酶/cAMP 依赖性蛋白激酶发挥作用，为视网膜短暂的横纹肌脱落做好准备。

• DOI: 10.1017/s0952523804215097
• 发表时间: 2004
• 期刊: Visual neuroscience
• 影响因子: 1.9
• 作者: Runyon,ScottL;Washicosky,KevinJ;Brenneman,RandallJ;Kelly,JeremyR;Khadilkar,RashmiV;Heacock,KevinF;McCormick,ShaelanM;Williams,KellyE;Jinks,RobertN
• 通讯作者: Jinks,RobertN

Central regulation of photosensitive membrane turnover in the lateral eye of Limulus. I. Octopamine primes the retina for daily transient rhabdom shedding.

鲎外侧眼光敏膜周转的中枢调节。

• DOI: 10.1017/s0952523802192066
• 发表时间: 2002
• 期刊: Visual neuroscience
• 影响因子: 1.9
• 作者: Khadilkar,RashmiV;Mytinger,JohnR;Thomason,LauraE;Runyon,ScottL;Washicosky,KevinJ;Jinks,RobertN
• 通讯作者: Jinks,RobertN