Faculty Profile:

Steven Bernstein, M.D., Ph.D.
Associate Professor

Opthalmology and Visual Sciences
School of Medicine

410-706-3712

slbernst@umaryland.edu

Research

My lab focuses on understanding mechanisms of neuronal aging and white matter-optic nerve stroke. White matter strokes correspond to approximately 40% of all strokes in the US, yet have been difficult to study in vivo. The optic nerve is actually an isolated CNS-white matter tract, and thus is excellent for studying questions of white matter stroke. My lab has generated the first clinically relevant models for optic nerve stroke (nonarteritic anterior ischemic optic neuropathy, NAION) in rodents and primates. The NAION models are the first in vivo stroke models that specifically targets white matter, and are relevant for one of the most common strokes affecting individuals. We use these models in a variety of species: to evaluate neuroprotective approaches to early stroke treatment, genetic response to white matter stroke, and primate-specific responses.

My research is also dedicated to identifying genes predisposing the retina to age-related neuronal diseases, such as macular degeneration. Our working hypothesis is that as neural tissues age, specific changes in gene expression occur that predispose or weaken the individual's ability to resist subtle gene differences and stress. We have identified a number of genes that change during aging, and are studying these gene's roles in contributing to age-related disease.

Lab Techniques

Current specific projects include mapping retinal neuron function and regeneration after stroke, and analysis of drugs that may be effective following stroke. We perform immunohistology, confocal microscopy, basic molecular biology (PCR and RNA-based PCR) and computer-aided stereotactic intracranial and intravitreal injections and evaluation of NAION by multiple electrophysiological methods.

Publications

Chen, C., Johnson, M.A., Slater, B.J., Flower, R.E., Miller, N.R., and Bernstein, S.L. (2008). A primate model of nonarteritic anterior ischemic optic neuropathy. Invest. Ophth. Vis. Sci., in press

Slater, BJ, Guo, Y., Mehrabyan, Z., Hunter, A., and Bernstein, S.L. (2008). Rodent anterior ischemic optic neuropathy (rAION) induces regional retinal ganglion cell apoptosis with a unique temporal pattern. In press, Invest. Ophth. Vis. Sci.

Bernstein, S.L., Mehrabyan, Z., Guo, Y., Moianie, N. (2007) Estrogen is not neuroprotective in a rodent model of optic nerve stroke. Molecular Vision 13, 1920-5

Bernstein, S.L., Guo, Y., Slater, B.J., Puche, A., and Kelman, S.E. (2007) Analysis of retinal ganglion cell stress and loss following optic nerve stroke in double reporter transgenic mice. Invest. Ophth. Vis. Sci. 48, 2304-2310

Bernstein, S.L., Koo, J-H., Slater, B.J., and Guo, Y. and Margolis, F.L., (2006) Analysis of optic nerve stroke by retinal Bex-1 expression. Molecular Vision, 12, 147-155

Goldenberg-Cohen, N., Cohen, Y., Guo, Y. Miller, N.R., Margolis, F.M. and Bernstein, S.L. (2005) Oligodendrocyte dysfunction following induction of experimental anterior ischemic optic neuropathy. Invest. Ophth.Vis. Sci. 43, 3677-3685

Wistow, G., Wyatt, K., David, L., Gao, C., Bateman, O., Bernstein, S.L., Tomarev, S., Segovia, L., Slingsby, C. and Viahtelic, T. (2005) Gamma N-crystallin and the evolution of the beta-gamma crystalline family in vertebrates. FEBS J. 272, 2276-2291

Hutcheson, K.A., Paluru, P.C., Bernstein, S.L., Koh, J., Rappaport, E.F., Leach, R.A., Young, T.L. (2005) Norrie disease gene sequence variants in an ethnically diverse population with retinopathy of prematurity. Mol. Vis. 11, 501-508

Ziesel AC, Bernstein SL, Wong PW. (2004). Functional and Genomic Analyses of Known Foveally-Expressed Genes. TIBETS 1:25-33.

Chowers I., Liu D., Farkas R., Gunatilaka T., Hackam A.S., Bernstein, S.L., Campochiaro P.A., Parmigian G., Zack D.J. (2003) Gene Expression Variation In Adult Human Retina. Hum. Mol. Genetics, 12, 2881-2893

Bernstein, S.L., Guo, G., Kelman, S.E., Flower, R.W., and Johnson, M.A. (2003).Cell function changes in early ischemic optic neuropathy. Invest. Ophth. Vis. Sci. 45, 1281-1288

Lagali, P.S., Liu, J., Ambasudhan, R., Kakuk, L.E., Bernstein, S.L., Seigel, G.M., Wong, P.W., Ayyagari, R. (2003) Evolutionarily conserved ELOVL4 gene expression in the vertebrate retina. Invest. Ophth. Vis. Sci . 44, 2841-2850

Ahmed, Z.M, Riazuddin, S., Ahmad, J., Bernstein, S.L., Guo, Y., Sabar, M.F., Sieving, P., Riazuddin, S., Griffith, A.J., Friedman, T.B., Belyantseva, I.A., and Wilcoz, E.R. (2003) PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23. Hum. Mol. Gen., 12, 3215-3223

Bhatti, R.A., Yu, S., Boulanger,A., Fariss, R.A., Guo, Y., Bernstein, S.L., Gentleman, S. and Redmond, T.M. (2003) Expression of Î²-carotene 15,15a monooxygenase in retina and RPE-Choroid. IOVS 44, 44-49

Wistow, G., Bernstein, S.L., Touchman, J.W., Bouffard, G., Wyatt, M.K., Peterson, K., Behal, A., Gao, J., Buchoff, P., Smith, D. (2002) Technical Brief: Grouping and identification of sequence tags (GRIST): Bioinformatics tools for the NEIBank database. Mol. Vis. 8, 164-170 (2002)

Wistow, G., Bernstein, S.L., Wyatt, M.K., Behal, A., Bouffard, G., Touchman, J.W., Smith, D., Peterson, K. (2002) Expressed sequence tag analysis of adult human lens for the NEIBank Project: Over 2000 non-redundant transcripts, novel genes and splice variants. Mol. Vis. 8,171-184

Wistow G., Bernstein S.L., Touchman J., Bouffard G., Wyatt M.K., Peterson K., Gao J., Gesuwan P., Smith D. Expressed sequence tag analysis of adult human iris for the NEIBank Project: Steroid-response factors and similarities with retinal pigment epithelium. Mol. Vis. 8, 185-195 (2002)

Wistow, G., Bernstein, S.L., Wyatt, M.K., Ray, S., Behal, A., Bouffard, G., Touchman, J.W., Smith, D., Peterson, K. (2002) Expressed sequence tag analysis of human retina for the NEIBank Project: Retbindin, an abundant, novel retinal cDNA and alternative splicing of other retina-preferred gene transcripts. Mol. Vis. 8, 196-204

Wistow, G., Bernstein, S.L., Wyatt, M.K., Fariss, R.N., Behal, A., Touchman, J.W., Bouffard, G., Smith, D., Peterson, K. (2002) Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: Over 6000 non-redundant transcripts, novel genes and splice variants. Mol. Vis. 8, 205-220 (2002)

Ahmed, Z.M., Riazuddin, S., Bernstein, S.L., Ahmed, Z., Khan, S., Griffith, A.J., Morell, R.J., Friedman, T.B., Riazuddin, S., Wilcox, E.R. (2001) Mutations of the protocadherin gene PCDH15 cause Usher type 1F. Am. J. Hum. Genet. 69, 25-34

Bernstein, S.L., Russell, P., Wong, P. Fishelevich, R. and Smith, L.E.H. (2001) Heat Shock Protein 90 in retinal ganglion cells: association with axonally transported proteins. Visual Neuroscience 18, 429-436

Bork, J.L., Peters, L.M., Riazuddin, S., Bernstein, S. L., Ahmed, Z.M., Ness, S.L., Polomeno, R., Ramesh, A., Schloss, M., Srikumari-Srisalapathy, C.R., Wayne, S., Bellman, S., Desmukh,D., Der Kaloustian, V.K., Lalwani, A., Riazuddin, S., Bitner-Glindzicz, M., Nance, W., Liu, X-Z., Wistow, G., Smith, R.J.H., Griffith, A.J., Wilcox, E., Friedman, T., Morell, R.J. (2001) Usher syndrome 1D (USH1D) and nonsyndromic recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am. J. Hum. Genet 68, 26-37.

Alexander, C., Bernstein, S.L., Rocchi, M., Auburger, G. (2001) Saturating density of STSs (1/6 kb) in a 1.1 Mb region on 3q28-q29: a valuable resource for cloning of disease genes. European Journal of Human Genetics 9, 307-310

Bernstein, S.L., Liu, M-H. and Somiari, R.I. (2000) Heat shock cognate-70 gene expression is altered during normal aging of the primate retina. Invest. Ophth. Vis. Sci. 41, 2857-2862

Hobby, P., Wyatt, M.K., Gan, W., Bernstein,S.L., Tomarev, S. Slingsby, C. and Wistow, G. (2000) Cloning, modeling, and chromosomal localization for a small leucine rich repeat proteoglycan (SLRP) family member expressed in human eye. Mol Vis 6, 62-78

P. Wong, B.A. Pfeffer, S.L. Bernstein, M.L. Chambers, Z.F. Zakeri, Y.Q. Wu, M.R. Wilson, S.P. Becerra (2000) Clusterin protein diversity in the primate eye. Molecular Vision 6, 184-191

Somiari, R.I., Wong, P. and Bernstein, S.L. (1999) High-density differential screening strategy for identification of fovea genes with altered expression in the retina during aging. Biotechnol. Biotechniques 13, 577-581

Bernstein, S.L. and Wong, P. (1998) Region specific expression of genes associated with human retinal diseases. Mol. Vis. 4, 24-35

Bernstein, S.L., Borst, D.E. and Wong, P. (1997) Region specific mitochondrial gene expression in the human retina. Mol. Brain Res. 744, 143-146

Bernstein, S.L., and Kempner, E. (1996) Radiation target analysis of ribozymes. Proc. Natl. Acad. Sci. U.S.A. 93, 6410-6414

Kempner, E.S., Salovey, R. and Bernstein, S.L. (1996) Radiation energy transfer in RNA polymers. Radiat. Phys. Chem. 48, 577-581

Bernstein, S.L., Borst, D.E., Neuder, M. and Wong, P. (1996) Characterization of a human fovea cDNA library and regional differential gene expression in the human fovea. Genomics 32, 301-308

Bernstein, S.L., Borst, D.E. and Wong, P. (1995) Isolation of differentially expressed human fovea genes and identification of gene candidates for human macular diseases. Molecular vision (1995) 1, 9005-9015

Personal History

Education

Undergraduate: Philadelphia College of Pharmacy and Science, Philadelphia, Pa., B.Sc. Microbiology (1975)

Graduate: Cornell University, New York Hospital, NYC, NY Ph.D. Neurobiology (1982) Thesis title: Changes in gene expression during the postnatal development of the rat cerebellum

Medical: SUNY-Downstate Medical Center, Brooklyn, NY M.D. (1985)

Postgraduate training: Medical College of Virginia, Richmond, VA: Ophthalmology Residency 1986-1989
Maimonides Medical Center, Brooklyn, NY: Medical Internship 1985-1986

National Eye Institute, Bethesda, MD: Senior Staff Fellow 1990-1996

National Eye Institute, Bethesda, MD: Ophthalmic Genetics Fellow 1990-1992

Research and Professional Experience

Assistant Professor, Dept. Ophthalmology; UMAB School of Medicine 1996-2002.

Associate Professor, Dept. Ophthalmology; UMAB School of Medicine 2002-Current.

Adjunct Assoc. Professor, Dept. Anatomy and Neurobiology, UMAB School of Medicine 2002-Current.

Adjunct Assoc. Professor, Dept. Genetics and functional Genomics 2002-Current.

Comprehensive Ophthalmologist, UMAB Department of Ophthalmology.

Director, Molecular Research Laboratory, Department of Ophthalmology.

Director, Ophthalmic Genetics Clinic.

Senior Staff Fellow, National Eye Institute, 1990-1996.

Ophthalmic Genetics Fellow, National Eye Institute, 1990-1992.

Ophthalmology Residency, Medical College Virginia, 1986-1989.

Medical Internship, Maimonides Medical Center, 1985-1986.

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