Effects of loss of sympathetic nerve activity on normal ocular aging

描述(由申请人提供)：在过去的50年里，平均寿命显著延长。然而，在许多组织中，对正常衰老过程的理解仍然存在很大差距。在通常与衰老相关的疾病方面已经取得了很大进展，然而，正常的衰老过程仍然是一个谜。受年龄影响很大的一个特定目标是眼睛。很明显，由于杆状感光器的丧失，夜视能力受到了损害。还有其他视网膜病理标志，如反应性米勒细胞和玻璃体形成。造成这些变化的机制尚不清楚。一个潜在的因素可能是交感神经活性的丧失，因为这通常会随着年龄的增长而发生。此外，手术切除幼年大鼠的交感神经会产生更多的炎症标志物和反应性Muller细胞，就像人类眼睛随着年龄的增长而发生的那样。因此，本项目的总体目标是确定交感神经传递调节脉络膜和视网膜功能随年龄增长的机制。这一建议的假设是，交感神经传递是正常的脉络膜和视网膜活动所必需的，当它随着年龄的增长而丧失时，在未患病的眼睛中会发生有害的过程。为了验证这些假说，实时定量聚合酶链式反应和蛋白质印迹分析将被用来研究从NIA获得的8、22和32月龄大鼠肾上腺素能受体基因和蛋白表达的变化。实验还将确定视网膜和脉络膜中的哪些细胞类型特别受正常衰老的影响。还将进行分析，以确定这些细胞变化是否会导致视网膜和脉络膜功能的丧失。还将研究老年大鼠的关键炎症和凋亡介质的基因和蛋白表达，并使用交感神经切除模型来确定衰老过程中出现的眼部并发症是否源于炎症过程。总体而言，这些研究将提供有关正常眼睛老化时可能起作用的机制的关键信息。有了这些信息，就有可能防止与年龄相关的视力丧失，或者为那些已经患有夜间视力下降和其他年龄导致的眼部病变的人恢复视力。 空

DESCRIPTION (provided by applicant): The average lifespan has significantly lengthened in the past 50 years. However, there are still large gaps in the understanding of the normal aging processes in a number of tissues. Much progress has been made on disease commonly associated with aging, yet, normal aging processes remain a mystery. One particular target that is substantially affected by age is the eye. It is clear that night vision is compromised through a loss of rod photoreceptors. There are also other markers of retinal pathology, such as reactive Muller cells and drusen formation. The mechanisms responsible for these changes are not clear. One potential factor may be a loss of sympathetic nerve activity, as this normally occurs with age. Furthermore, surgical sympathectomy in a young rat produces increased inflammatory markers and reactive Muller cells, much like occurs in the human eye with increasing age. Therefore, the overall goal of this project is to determine the mechanisms by which sympathetic neurotransmission regulates choroidal and retinal functioning with increasing age. The hypothesis of this proposal is that sympathetic neurotransmission is required for normal choroidal and retinal activities and upon its loss with age, detrimental processes occur in a non- diseased eye. To test these hypotheses, real-time PCR and western blot analysis will be used to investigate changes in adrenergic receptor gene and protein expression in 8, 22, and 32 month old rats obtained from NIA. Experiments will also determine which cell types in the retina and choroid are particularly affected by normal aging. Analyses will also be done to determine if these cellular alterations results in a loss of function in the retina and choroid. Gene and protein expression will also be investigated for key inflammatory and apoptotic mediators in aged rats and using the sympathectomy model to determine whether the ocular complications noted in aging result from inflammatory processes. Overall, these studies will provide critical information as to potential mechanisms in play as the normal eye ages. With this information, it may be possible to prevent age-related vision loss or restore vision to those already suffering from reduced night vision and other ocular pathology from age. null