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Alison C Ziesel, Daniel T Organisciak, Micah A Chrenek, Paul Wong; Circadian regulated genes underlying retinal susceptibility and resistance to light-induced damage. Invest. Ophthalmol. Vis. Sci. 2014;55(13):425.
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Light-induced retinal damage has long served as a model of retinal dysfunction and visual cell loss due to inherited disease or caused by oxidative stress. Numerous extrinsic factors are known to influence the extent of visual cell loss. Visual cell damage is also affected by intrinsic factors, including circadian rhythms. The purpose of the current study is to screen for circadian related factors that affect visual cell loss.
Gene profiles were generated for both dark-reared and cyclic light-reared animals using standard methodologies. Retinal tissues taken at 1 am, 9 am, and 5 pm were analyzed. For dark-reared animals 1 am and 9 am define light-induced damage (LID) susceptible periods, while 5 pm defines a LID resistant period. In the case of cyclic light-reared animals 1 am defines a LID susceptible period, while 9 am and 5 pm define LID resistant periods. We took a comparative analysis to screen for changes at the level of gene expression to see if there were any conserved events between LID resistance and susceptibility. These results in turn were compared from one profiling study to the other to examine for consistencies in fold changes, FC.
13 genes were consistently repressed during the LID susceptible state as compared to the resistant state. 17 genes were consistently elevated during the LID susceptible state as compared to the resistant state. We regard these 30 genes as those that putatively define retinal susceptibility/resistance to light-induced damage and an ontological interrogation of these genes was undertaken. Gene products for 15 of the 30 LID susceptibility/resistance genes fall into a single functional protein network. Included in this network is DRD4 the functional product of the dopamine receptor D4 gene (Drd4).
With respect to retinal susceptibility/resistance to light damage we have found consistent changes in 30 genes. The identification of Drd4 as one of these genes provides some validation to the authenticity of these LID retinal susceptibility/resistance genes. In mice with a disruption of the Drd4 gene, cyclic AMP levels in the dark-adapted retina are significantly lower compared to wild-type retina, unresponsive to light, and resistant to light-induced damage (Dr. M. Iuvone, Emory University, personal communication, 2013).
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