| First Author | Bakalash S | Year | 2011 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 52 |
| Issue | 12 | Pages | 9033-46 |
| PubMed ID | 21969301 | Mgi Jnum | J:189462 |
| Mgi Id | MGI:5445841 | Doi | 10.1167/iovs.11-7498 |
| Citation | Bakalash S, et al. (2011) Egr1 expression is induced following glatiramer acetate immunotherapy in rodent models of glaucoma and Alzheimer's disease. Invest Ophthalmol Vis Sci 52(12):9033-46 |
| abstractText | PURPOSE: Immunization with glatiramer acetate (GA) alleviates the neuropathology associated with glaucoma and Alzheimer's disease (AD) in rodent models. This research was undertaken to screen for molecular factors underlying GA-induced neuroprotective mechanisms in these models of chronic neurodegeneration. METHODS: Gene expression profiles were analyzed in GA-immunized versus nonimmunized elevated-intraocular pressure (IOP) rat models of glaucoma by using whole genome cDNA microarrays and were further validated by quantitative real-time PCR analysis. A gene, prominently upregulated by GA in elevated IOP retina, was further studied in APP(SWE)/PS1(DeltaE9)-transgenic (AD-Tg) mice after GA immunization. RESULTS: Seven days after treatment with GA, numerous genes were regulated in the retinas of rats with elevated IOP. Comprehensive functional classification and DAVID/KEGG enrichment analysis of GA-induced differentially expressed genes revealed annotation terms and pathways involved in neuroprotection, immune responses, cell communication, and regeneration. Specifically, increased mRNA levels of an early growth response (Egr) 1 gene were evident in GA-immunized retinas with elevated IOP. In AD-Tg mice, a significant increase in hippocampal EGR1 protein levels was also found in response to GA immunization. Nuclear EGR1 in the dentate gyrus colocalized more frequently with doublecortin-positive and Ki67 proliferating neural progenitors in GA-immunized as compared to nonimmunized AD-Tg mice. Further, EGR1 levels were negatively correlated with hippocampal amyloid-beta plaque burden. CONCLUSIONS: This study presents global gene expression profiles associated with GA immunization in a glaucoma rat model. Moreover, it identifies EGR1 transcription factor as a potential mediator for GA-induced neuroprotection in both glaucoma and AD. |
