Professor - Department of Ophthalmology, the Camille and Raymond Hankamer Chair in Ophthalmology Professor - Department of Neuroscience Professor - Department of Molecular Physiology and Biophysics Ph.D., Harvard University, 1979 Cullen Eye Institute Baylor College of Medicine, NC-205 Houston, Texas 77030 Telephone: 713-798-5966 - Fax: 713-798-6457 Email: swu@bcm.tmc.edu Website: neuro.bcm.edu/wu

The research interests of our laboratory concern molecular mechanisms underlying synaptic transmission and neural function in the brain.  We use the vertebrate retina as a model system because of its accessibility, its known function, and its accurately controllable natural input.  Our overall goal is to understand how synaptic events in the retina encode and process various attributes of visual images (such as brightness, ON/OFF signals, contrast, shape, motion and color) and to elucidate how cellular, synaptic, and genetic factors cause retinal dysfunction in diseased states.

There are three research projects in our laboratory:

(1) By using microelectrode, patch clamp, and optical recording techniques in conjunction with immunocytochemistry, fluorescent dye injection, and confocal and electron microscopy, we study synaptic circuitry mediating visual information processing in amphibian and mammalian retinas.  We focus our studies on how ion channels, neurotransmitter receptors and transporters, and second messengers in individual retinal synapses mediate rod/cone inputs, ON/OFF signals, and the center-surround receptive field organization of bipolar cells and ganglion cells.  We also examine how synaptic plasticity occurs in the retina and how retinal signals are modulated by visual adaptation.  Additionally, we correlate various attributes of bipolar cell, amacrine cell, and ganglion cell light responses with their morphology, especially the patterns of axonal and dendritic stratification in the inner plexiform layer.  This allows us to derive computational algorithms for signal segregation and integration in the visual system.

(2) We study gene regulation of retinal function and eye disorders in genetically manipulated mouse models by using electroretinogram (ERG), patch clamp recording, immunocytochemistry, and molecular biological techniques. The mouse models we studied include that with a deletion of the transcription factor gene BETA2/NeuroD, a model for spinocerebellar ataxia type 7, the GCAP knockout and knock-in mice and a BBS (Bardet-Biedl Syndrome) knockout mouse model. We examined how various transcription factors and proteins affect the structure and function of individual retinal cells, and how they may mediate degenerative diseases in the retina.

(3) We also study the mechanisms of neuroprotection of retinal ganglion cells in glaucoma.  Glaucoma is a leading cause of irreversible blindness in the US and throughout the world.  It is associated with elevated intraocular pressure (IOP) and an end result of retinal ganglion cell death.  We are interested in understanding how various pathological conditions affect retinal ganglion cell function and also what pharmacological and genetic tools can be used to prevent or slow down the degenerative process of retinal ganglion cells in glaucoma.  We have recently developed a mouse glaucoma model, by photocoagulating the episcleral and limbal veins, and found that this procedure causes elevation of IOP and ganglion cell loss in a pattern very similar to glaucoma.  We use this mouse model to test the long-term neuroprotective effects of endogenous molecules whose expression levels are genetically altered. This allows us to identify endogenous molecules and neurotrophic factors that may prevent or slow down vision loss in glaucoma.

In summary, we simultaneously employ electrophysiological, pharmacological, anatomical, and molecular genetic techniques in order to study how electrical and chemical synapses in the retina process visual signals.  We also employ these techniques in order to study how various physiological, biochemical, and genetic factors regulate retinal function and dysfunction.  We hope to integrate our results into a comprehensive and coherent description of how individual molecular and synaptic events in the retina mediate visual information processing and eye disorders.  Such a description will not only set a firm foundation for visual science, but it will also serve as a model system for studying how the entire brain functions.

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Wu, S.M., Gao, F. and Maple, B.R. (2000) Functional architecture of synapses in the inner retina: segregation of visual signals by stratification of bipolar cell axon terminals. J. Neuroscience, 20, 12, 4462- 4470.

Pang, J. J., Gao, F. and Wu, S.M. (2002) Segregation and integration of visual channels: layer-by-layer computation of ON-OFF signals by amacrine cell dendrites. J. Neuroscience, 22 (11), 4693-4701.

Pennesi, M.E., Howes, K.A., Baehr, W., and Wu, S.M. (2003) GCAP1 rescues cone photoreceptor responses in GCAP1/GCAP2 knockout mice. Proc. Nat. Acad. Scien. (USA) 100, 11, 6783-6788.

Pang, J. J., Gao, F. and Wu, S. M. (2003) Light-evoked excitatory and inhibitory synaptic inputs to ON and OFF a ganglion cells in the mouse retina. J. Neuroscience 23, 14, 6063-6073.

Zhang, J. and Wu, S.M. (2004) Connexin35/36 gap junction proteins are expressed in photoreceptors of the tiger salamander retina. J. Comp. Neurol. 470, 1-12.

Pang, J.J., Gao, F. and Wu, S. M. (2004) Stratum-by-stratum projection of light response attributes by retinal bipolar cells. J. Physiology, 558.1, 249-262.

Pang, J. J., Gao, F. and Wu, S. M. (2004) Light-evoked current responses in rod bipolar cells, cone depolarizing bipolar cells, and AII amacrine cells in dark-adapted mouse retina. J. Physiology. 558.3, 897-912.

Bramblett, D.E., Pennesi, M.E., Wu, S.M. and Tsai, M.J. (2004) Bhlhb4 in rod bipolar cell maturation. Neuron, 43,6,779-793.

Zhang, J. and Wu, S.M. (2005) Physiological properties of rod photoreceptor coupling in the tiger salamander retina. J. Physiology, 564.3, 849-862.

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Sam and Bertha Brochstein Award for Outstanding Achievement in Retina Research, Retina Research Foundation, 1987.

Dolly Green Scholars Award, Research to Prevent Blindness, Inc. 1989.

Marjorie W. Margolin Prize, Retina Research Foundation, 1991.

Senior Scientific Investigators Award, Research to Prevent Blindness, Inc. 1997.

James M. Barr Award for Outstanding Retina Research in the Greater Houston Area, Retina Research Foundation, 1998.

James M. Barr Award for Outstanding Retina Research Achievement, Retina Research Foundation, 2005.

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• Cameron Cowan (Neuroscience)
• David Simons (Neuroscience)
• Ai-jun Zhang

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Preparation of living retinal slices for patch clamp recordings under infrared illumination.

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