Effects of loss of sympathetic nerve activity on normal ocular aging

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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