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M. Rosario Hernandez, DDSGeorge and Edwina Tarry Professor of Ophthalmology
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The molecular mechanism of axonal degeneration in neurological disease is poorly understood. Glaucoma is a chronic blinding disease associated with elevated intraocular pressure (IOP). The mechanism of retinal ganglion cell (RGC) degeneration is unknown but the site of injury is at the level of the optic nerve head (ONH). Our recent work indicates that the cells supporting RGC axons in the ONH, the astrocytes, may be responsible for several of the damaging effects of elevated pressure in glaucoma.
Our current studies aim to:
1. Identify variations in gene expression in ONH astrocytes that may underlie susceptibility to optic nerve damage in African Americans, a population at high risk for developing glaucoma, compared to age-matched Caucasians.
2. Identify pressure specific mechanisms which regulate the transition and the maintenance of the reactive astrocyte phenotype in neural degeneration by comparing responses to different stimuli, hydrostatic pressure, oxidative stress and proinflammatory cytokines.
3. Characterize the molecular interactions between astrocytes and axons in the optic nerve that lead to a non-supportive environment that prevents axon survival and underlies progression of optic neuropathies.
Our studies use microarray analysis, bioinformatic, functional assays, specific genetic and pharmacological inhibition of pathways, confocal and electron microscopy, biochemical analysis, molecular biology, culture of human astrocytes and neurons, human ONH tissue, monkeys and mice.
Bajenaru ML, Garbow JR, Perry A, Hernandez MR, Gutmann DH. Natural History of Neurofibromatosis 1-Associated Optic Nerve Glioma Formation in Mice. Ann Neurol. 2005, 57 (1):119-27.
Hashimoto, K, Parker, A, Malone, P, Gabelt, B.T, Kaufman, P.S, Hernandez, M.R. Long Term Activation of c-Fos and c-Jun in Optic Nerve Head Astrocytes in Experimental Ocular Hypertension in Monkeys and after Exposure to Elevated Pressure in vitro. Brain Res. 2005, 1054 103-115.
Agapova OA, Gabelt BT, Rasmussen C, Kaufman PL, Hernandez MR. Androgen Receptor and NFκB Expression in Human Normal and Glaucomatous Optic Nerve Head Astrocytes in vitro and in Experimental Glaucoma. Exp. Eye Res. 82, June 2006, Pages 1053-1059 .
Vázquez-Chona FR, Khan AN, Chan CK, Moore AN, Dash, PK, Hernandez MR, Lu L, Chesler EJ, Manly KF, Williams RW, Geisert EE Jr. Genetic networks controlling retinal injury. Mol Vis. 2005 4; 11: 958-970.
Agapova OA, Malone PA, Hernandez MR. A Neuroactive Steroid 5α-androstane-3α, ß-diol Regulates Androgen Receptor Level in Astrocytes. J. Neurochem. 2006, Vol. 8, Page 355.
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View Publications by Rosario Hernandez listed in the National Library of Medicine (PubMed). |
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