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的差距。在与衰老有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，夜间视力是通过杆光感受器的损失而受损的。还有视网膜病理学的其他标志物，例如反应性Muller细胞和玻璃疣形成。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动的丧失，因为这通常会随着年龄的增长而发生。此外，年轻大鼠的交感神经切除术产生增加的炎症标记物和反应性Muller细胞，很像随着年龄的增长发生在人眼中。因此，本项目的总体目标是确定交感神经传递随年龄增长调节脉络膜和视网膜功能的机制。该提议的假设是交感神经传递是正常脉络膜和视网膜活动所需的，并且在其随年龄丧失时，在未患病的眼睛中发生有害过程。为了检验这些假设，将使用实时PCR和蛋白质印迹分析来研究从NIA获得的8、22和32月龄大鼠中肾上腺素能受体基因和蛋白质表达的变化。实验还将确定视网膜和脉络膜中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改变是否导致视网膜和脉络膜功能丧失。还将研究老年大鼠中关键炎症和凋亡介质的基因和蛋白质表达，并使用交感神经切除术模型来确定衰老中注意到的眼部并发症是否由炎症过程引起。总的来说，这些研究将提供关键信息，作为正常眼睛年龄的潜在机制。有了这些信息，就有可能预防与年龄有关的视力丧失，或者恢复那些已经患有夜间视力下降和其他眼部疾病的人的视力。

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.