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，平均寿命明显延长。然而，在许多组织的正常老化过程的理解仍然有很大的差距。人们在研究与衰老相关的疾病方面取得了很大进展，然而，正常的衰老过程仍然是个谜。受年龄影响最大的一个目标是眼睛。很明显，夜视是由于杆状光感受器的缺失而受损的。还有其他视网膜病理标记，如反应性穆勒细胞和囊肿形成。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，因为这通常随着年龄的增长而发生。此外，年轻大鼠的交感神经切除手术会产生更多的炎症标志物和反应性穆勒细胞，就像随着年龄的增长在人眼中发生的一样。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脉络膜和视网膜正常活动所必需的，随着年龄的增长，交感神经传递的丧失会在未患病的眼睛中发生有害的过程。为了验证这些假设，我们将采用实时荧光定量PCR和western blot分析方法研究8、22和32月龄NIA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，以确定这些细胞改变是否会导致视网膜和脉络膜功能丧失。我们还将研究衰老大鼠关键炎症和凋亡介质的基因和蛋白表达，并利用交感神经切除模型来确定衰老过程中眼部并发症是否由炎症过程引起。总的来说，这些研究将为正常眼睛老化的潜在机制提供关键信息。有了这些信息，就有可能预防与年龄有关的视力丧失，或使那些已经患有夜视和其他眼部疾病的人恢复视力。

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. null