Preserving the Precious Gift of Sight

Samuel M. Wu, PhD

KAYSER RESEARCH PROJECT

Cullen Eye Institute

Baylor College of Medicine

Houston, TX

 

Dr. Wu’s Research Project

Pharmacological and Genetic Mechanisms Underlying Retinal Cell Death in Glaucoma and Age-related Macular Degeneration

Major Awards

2011 Alcon Research Institute Award

2009 Friedenwald Award (Association for Research in Vision and Ophthalmology)

2008 Ludwig von Sallmann Prize (International Society for Eye Research)

Current Research Interests

Dr. Wu’s research project is to study cellular, synaptic and genetic mechanisms underlying retinal cell dysfunction and degeneration in glaucoma and age-related macular degeneration (AMD). By using the multi-electrode array system and reverse correlation methods, his lab has developed new recording and analytic tools for studying spatiotemporal receptive field properties of retinal ganglion cells (RGCs). There are three specific aims: (1) to study spatiotemporal properties and response sensitivity of retinal ganglion cells (RGCs) in the mouse retina, and how light-evoked responses of RGCs change in disease states, such as AMD and glaucoma. (2) to characterize ON-center/OFF-surround and OFF-center/ON-surround RGC receptive fields in normal, mutant and diseased mouse retinas. They will use spike-trigger-average (STA) and white noise checkerboard stimulation methods to map receptive fields of various types of RGCs. (3) to study the effects of elevated intraocular pressure (IOP) on center-surround antagonistic receptive fields of retinal ganglion cells. Since elevated IOP is known to be associated with glaucoma, these studies will provide crucial information on how RGC receptive fields are altered in glaucoma patients. Moreover, techniques and analytical tools developed in this project can be used as common techniques and general analytical framework to investigate how center-surround receptive fields are altered in other disease states.

Progress in 2016

Dr. Wu’s lab published 5 papers and submitted four manuscripts in top international journals. These publications report their new discoveries on how rod and cone signaling pathways mediate light responses and receptive fields of various types retinal ganglion cells (RGC), and how dysfunction of bipolar cell and amacrine cell synapses affect retinal degeneration in glaucoma, AMD and retinitis pigmentosa (RP). In collaboration with Dr. Wensel’s lab, Dr. Wu’s group also studied how light regulates phosphatidylinositol-3-phosphate in retinal rods. Dr. Wu and his lab members gave 6 presentations at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in May, 2016 in Seattle, WA, and 1 presentation at the FASEB meeting in July, 2016 in Denver, CO.

Plans for 2017

Dr. Wu’s group will continue studying mechanisms underlying retinal ganglion cell dysfunction in glaucoma and rod/cone pathway damage in AMD. His lab will develop new multi-electrode array system and data acquisition/analysis software that allows high throughput investigation on spatiotemporal response profiles of simultaneously recorded retinal ganglion cells. They will also develop new computerized optokinetic reflex recording system to study changes in motion sensitivity of visual neurons in healthy and diseased retinas. Moreover, they will study center-surround receptive field organization of various types of retinal ganglion cells, and how glaucomatous and AMD insults alter receptive fields of retinal ganglion cells.

Progress in 2015

Dr. Wu’s lab published 5 papers and submitted three additional manuscripts in top international journals. These publications report their new discoveries on how retinal ciliopathy gene affects retinal disease progression, how elevation of intraocular pressure results in retinal ganglion cell sensitivity decrease and cell loss in glaucoma, how elevated intracranial pressure (ICP) causes optic nerve and retinal ganglion cell degeneration, and how protein kinase C α (PKCα) modulates rod bipolar cell function in the mammalian retina. Dr. Wu and his lab members gave 6 presentations at the ARVO annual meeting in May, 2015 in Denver, CO, and one presentation at the Society for Neuroscience meeting in October, 2015 in Chicago, IL.

Progress in 2014

Dr. Wu’s lab published 3 papers and submitted four manuscripts in top international journals. These publications report their new discoveries on how various isoforms of glutamate transporters affect signal transmission from photoreceptors to second-order retinal neurons, and how dysfunction of the photoreceptor output synapses may mediate retinal degeneration in glaucoma, AMD and retinitis pigmentosa (RP). Dr. Wu and his lab members gave 4 presentations at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in May, 2014 in Orlando, Florida and one presentation at the International Society for Eye Research meeting in July, 2014 in San Francisco, California.

Progress in 2013

During the past year, Dr. Wu’s lab published four papers in top international journals including Investigative Ophthalmology and Visual Sciences, and Journal of Physiology. These publications report new discoveries on new animal models for glaucoma, AMD and retinitis pigmentosa (RP), as well as physiological and pharmacological properties of healthy and diseased retinal neurons. Dr. Wu and his lab members gave four presentations at the Association for Research in Vision and Ophthalmology (ARVO) 2013 annual meeting in Seattle, and presented two keynote lectures at two International Symposia of Ophthalmology in November, 2013 in Guangzhou and Beijing, China.

 

Confocal image of a flat-mounted retina of a ChAT-cre fluorescence mouse, in which all cholinergic amacrine cells show red fluorescence. A starburst amacrine cell (arrow) and a sustained OFF alpha ganglion cell (sOFFαGC) were filled with neurobiotin (green) via whole-cell patch electrodes. Calibration bar: 10µm
 

Progress in 2012

Dr. Wu’s lab published 5 papers in top international journals including, Investigative Ophthalmology and Visual Sciences, Journal of Physiology, Vision Research and Human Molecular Genetics. These publications report new discoveries on new animal models for retinitis pigmentosa (RP) and Leber congenital amaurosis, as well as physiological and pharmacological properties of healthy and diseased mouse retinal neurons. Dr. Wu and his lab members gave 4 presentations at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in May, 2012 at Ft. Lauderdale, Florida, and 1 presentation at the International Society of Eye Research (ISER) meeting in July, 2012 in Berlin, Germany.

Dr. Wu continued his highly successful research in studying mechanisms of retinal degeneration and developing new gene therapy vectors for BBS, AMD and glaucoma patients. Additionally, his group studied synaptic mechanisms underlying retinal ganglion cell death in acute and chronic glaucoma models, and developed and constructed new non-invasive devices for early detection/diagnosis of AMD and glaucoma in animals and humans.

Dr. Wu’s research is focused on molecular and synaptic mechanisms underlying retinal cell death in age-related macular degeneration (AMD) and glaucoma, and to develop new gene therapy vectors for rescuing retinal degeneration in these diseases.

His group has been successful in demonstrating that gene therapy prevents photoreceptor degeneration in a Bardet-Biedl Syndrome mouse model, and in developing a new microinjection system for ocular delivery of pharmacological agents and viral/gene conjugates. His lab also designed new non-invasive devices for early detection of photoreceptor and ganglion cell dysfunction in animals and humans. They use these new tools in conjunction with electrophysiological and pharmacological techniques to develop new treatment and prevention strategies for fighting human AMD and glaucoma.

Confocal microscope photo of mouse retinal bipolar cells filled with Lucifer yellow (red) and counter-stained with PKCa (green) and ChAT (blue)

Progress in 2011

Dr. Wu’s lab published 4 papers in top international journals including Proceedings of the National Academy of Sciences (USA), Molecular and Cellular Biology, Investigative Ophthalmology and Visual Sciences and Journal of Comparative Neurology.

These publications report new discoveries on the first successful gene therapy that prevents photoreceptor degeneration in a Bardet Biedl Syndrome (BBS) animal model, and on physiological, pharmacological and genetic properties of healthy and diseased mouse retinas. BBS is a devastating blinding disease for children, and this is a ground-breaking study in developing a successful gene therapy protocol for rescuing photoreceptors in BBS.

The first successful gene therapy for this blinding disease, Dr. Wu’s study constitutes a major step towards a cure for BBS in human patients. Using a tiny benign virus to take a missing gene to the rods and cones of the retina in the mice with this syndrome, Dr. Wu’s lab was able to demonstrate that blindness was prevented. Photoreceptors that were treated survived, and after the gene therapy mice that had been treated responded to visual stimuli.

Dr. Wu and his lab members gave 6 presentations in the Association for Research In Vision and Ophthalmology (ARVO) annual meeting in May, 2011, at Ft. Lauderdale, Florida.

Sam Wu, PhD, imaging retinal sections in preparation for electrophysiological recordings from mutant and diseased retinal neurons
Sam Wu, PhD, imaging retinal sections in preparation for electrophysiological recordings from mutant and diseased retinal neurons
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Mission of RRF

The mission of the Retina Research Foundation is to reduce retinal blindness worldwide by funding programs in research and education. As a public charity, RRF raises funds from the private sector and the investment of its endowment funds.

RRF’s 48th Anniversary

October 1, 2017