This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age related changes in the function and structure of the tears producing lacrimal gland is postulated to be contributed by progressive reduction in parasympathetic innervation. The goal is to identify target genes that are essential in controlling lacrimal gland tear production and secretion, and to elucidate cellular networks that are altered with age and those that displayed neural-specific regulation. Genome-wide gene expression profile in young and aged rat lacrimal gland under normal aging, neural ablation, and overstimulation of the lacrimal gland response were generated using GeneChip Rat Genome 230 2.0 arrays. Expression data were filtered using ANOVA (p1.5 fold). The MetaCore systems biology platform was used to identify common and unique genes under different ages and neural manipulations. Sub-networks of expression data and sub-networks of transcription regulation were generated based on a priori knowledge and interpreted using gene ontology enrichment. Significant genes confirmed by real time RT-PCR or Western blot analysis were used as """"""""reference targets"""""""" to evaluate the different networks. With age and neural ablation, downregulated genes (83 transcripts) were almost three times greater than for upregulated genes (33 transcripts). The magnitude of change was greater for the downregulated genes. Several cellular targets that may serve as biomarkers to assess lacrimal gland function and putative tear proteins were also identified. Due to the limitations of microarray data, further experiments (ie.ChIP-PCR) will be needed in order to validate the cellular and transcription networks that are implicated in lacrimal gland gene response to different neural manipulations.
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