LACRIMAL GLAND BIOINFORMATICS: A NEURAL CONNECTION OF DRY EYE AND AGING

这个子项目是众多研究子项目之一

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. It is hypothesized that the ability to activate the afferent, sensory pathway to affect lacrimal gland response is diminished with age and affect gene transcription response. Fischer rats (4 and 24 months) received unilateral corneal wound to stimulate continuous tearing and after 12 hours, lacrimal glands were removed for DNA microarray analysis using the Affymetrix rat genome 230 2.0 GeneChip. Expression data were normalized using the RMA method and analyzed in GeneSpring GX. The two-way ANOVA (p0.01) for age and wounding factors were applied and identified 137 transcripts that were significant with age, 117 transcripts with wounding, and 23 transcripts that showed wounding effect with age. However, the magnitude of fold change for these transcripts was notably small. Seven transcripts were found at the 1.5 fold cutoff for the 4 vs. 24 month wounded, most notably the increased expression of the cAMP-dependent protein kinase inhibitor beta. For the 4 vs. 24 month unwounded, 26 transcripts were found, most notably fibronectin 1 and casein kinase 2. Gene ontology analysis for over-representation of molecular function for genes in the age or wounding effects found transferase and protein transporter activity in the age effect, and for the wounding effect motor and ligase activity. Integrase and isomerase activity were found for the interaction effect. The magnitude of gene response after 12 hours in the lacrimal gland as a function of age was very minimal. It is probable that the magnitude of change could be greater and more appropriate at an earlier time point.