NDLI: Egr1 expression is induced following glatiramer acetate immunotherapy in rodent models of glaucoma and Alzheimer's disease.

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Egr1 expression is induced following glatiramer acetate immunotherapy in rodent models of glaucoma and Alzheimer's disease.

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Egr1 expression is induced following glatiramer acetate immunotherapy in rodent models of glaucoma and Alzheimer's disease.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kramerov, Andrei Berel, Dror Koronyo-Hamaoui, Maya Koronyo, Yosef Bakalash, Sharon Seidenberg, Hillary Black, Keith L. Pham, Michael Salumbides, Brenda C.
Description	Country affiliation: United States Author Affiliation: Bakalash S ( Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA.)
Abstract	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(ΔE9)-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-ß 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.
ISSN	01460404
e-ISSN	15525783
Journal	Investigative Opthalmology & Visual Science
Issue Number	12
Volume Number	52
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2011-11-21
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Alzheimer Disease Drug Therapy Early Growth Response Protein 1 Genetics Glaucoma Immunosuppressive Agents Pharmacology Peptides Immunology Animals Chronic Disease Disease Models, Animal Gene Expression Drug Effects Glatiramer Acetate Hippocampus Physiology Mice Mice, Transgenic Nerve Degeneration Neuroprotective Agents Oligonucleotide Array Sequence Analysis Rats, Inbred Lew Real-time Polymerase Chain Reaction Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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