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Theodore Leng

Publications and source records attributed to Theodore Leng.

6 recordsLinked to original sources
PubMed2006

A model retinal interface based on directed neuronal growth for single cell stimulation.

In this work, we use cell micropatterning technologies to direct neuronal growth to individual electrodes, and demonstrate that such an approach can achieve selective stimulation and lower stimulation thresholds than current field-effect based retinal prostheses. Rat retinal ganglion cells (RGCs) were purified through immunopanning techniques, and microcontact printing (microCP) was applied to align and pattern laminin on a microelectrode array, on which the RGCs were seeded and extended neurites along the pattern to individual electrodes. The stimulation threshold currents of RGCs micropatterned to electrodes were found to be significantly less than those of non-patterned RGCs over a wide range of electrode-soma distances, as determined with calcium imaging techniques. Moreover, the stimulation threshold for micropatterned cells was found to be independent of electrode-soma distance, and there was no significant effect of microCP on cell excitability. The effects of additional stimulation parameters, such as electrode size and pulse duration, on threshold currents were determined. The stimulation results quantitatively demonstrate the potential benefits of a retinal prosthetic interface based on directed neuronal growth.

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PubMed2004

The chick chorioallantoic membrane as a model tissue for surgical retinal research and simulation.

PURPOSE: We describe the use of chick chorioallantoic membrane (CAM) as a model system for the study of the precision and safety of vitreoretinal microsurgical instruments and techniques. METHODS: The CAM was prepared for experimentation with and without its inner shell membrane (ISM) attached for in vivo and in vitro experiments that simulated medical and surgical interventions on the retina. RESULTS: The CAM's ease of use, low cost, and anatomic structure make it a convenient model for surgical retinal and retinal vascular modeling. CONCLUSION: While CAM has been used extensively in the past for ocular angiogenesis studies, we describe the tissue as a useful tool for a variety of other applications, including (1) testing of novel surgical tools and techniques for cutting and coagulating retina and its vasculature, (2) testing vessel cannulation and injection techniques, (3) angiographic studies, and (4) endoscopic surgery.

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PubMed2004

Directed retinal nerve cell growth for use in a retinal prosthesis interface.

PURPOSE: Retinal prosthetic devices that use microelectrode arrays to stimulate retinal nerve cells may provide a viable treatment for degenerative retinal diseases. Current devices are based on electrical field-effect stimulation of remaining functional neural elements. However, the distance between target neurons and electrodes limits the potential density of electrodes and the ability to stimulate specific types of retinal neurons that contribute to visual perceptions. This study was conducted to investigate the use of microcontact printing (muCP) to direct cultured or explant retinal ganglion cell (RGC) neurites to precise and close stimulation positions and to evaluate the cell types that grow from a retinal explant. METHODS: RGCs and whole retinal explants were isolated from postnatal day-7 Sprague-Dawley rats using immunopanning purification and microdissection, respectively. Aligned muCP was used to direct the growth of RGC neurites from pure cultures (n=105) and retinal explants (n=64) along laminin patterns and to individual microelectrodes. Immunofluorescence stains (n=39) were used to determine the cell types that grew out from the retinal explants. RESULTS: RGC neurite growth was directed reproducibly along aligned laminin micropatterns to individual microelectrodes in pure RGC cultures and from full-thickness explanted rat retinas in 92% of experiments, neurites from pure RGC cultures extended along the laminin lines with an average length of 263 +/- 118 microm (SD; n=27) after 24 hours. Neurites from retinal explants extended in more than 80% of experiments and were observed to grow to an average length of 279 +/- 78 microm (n=64) after 2 days in culture. These neurites grew up to 3 mm after 1 month of culture on the laminin micropatterns. Immunohistochemical stains demonstrated that extended processes from both RGCs and glial cells grew out of retinal explants onto stamped laminin lines. CONCLUSIONS: Using muCP to pattern surfaces with growth factors, individual neuronal processes from pure RGC culture and whole retinal explants can be directed to discrete sites on a microelectronic chip surface. By directing RGC neurite processes to specific sites, single cell stimulation becomes possible. This may allow discrete populations of retinal neurons to be addressed so that physiologic retinal processing of visual information can be achieved.

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PubMed2003

The Artificial Synapse Chip: a flexible retinal interface based on directed retinal cell growth and neurotransmitter stimulation.

The Artificial Synapse Chip is an evolving design for a flexible retinal interface that aims to improve visual resolution of an electronic retinal prosthesis by addressing cells individually and mimicking the physiological stimulation achieved in synaptic transmission. We describe three novel approaches employed in the development of the Artificial Synapse Chip: (i) micropatterned substrates to direct retinal cell neurite growth to individual stimulation sites; (ii) a prototype retinal interface based on localized neurotransmitter delivery; and (iii) the use of soft materials to fabricate these devices. By patterning the growth of cells to individual stimulation sites, we can improve the selectivity of stimulation and decrease the associated power requirements. Moreover, we have microfabricated a neurotransmitter delivery system based on a 5- micro m aperture in a 500-nm-thick silicon nitride membrane overlying a microfluidic channel. This device can release neurotransmitter volumes as small as 2 pL, demonstrating the possibility of chemical-based prostheses. Finally, we have fabricated and implanted an equivalent device using soft flexible materials that conform to the retinal tissue more effectively. As many of the current retinal prosthesis devices use hard materials and electrical excitation at a lower resolution, our approach may provide more physiologic retinal stimulation.

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PubMed2002

Microcontact printing on human tissue for retinal cell transplantation.

OBJECTIVES: To demonstrate that microcontact printing, a modern materials fabrication technique, can be used to engineer the surface of human tissue and to show that inhibitory molecules can be used to pattern the growth of retinal pigment epithelial cells or iris pigment epithelial cells on human lens capsule for transplantation. METHODS: Photolithographic techniques were used to fabricate photoresist-coated silicon substrates into molds. Poly(dimethylsiloxane)stamps for microcontact printing were made from these molds. The poly(dimethylsiloxane) stamps were then used to "wet-transfer" growth inhibitory molecules to the surface of prepared human lens capsules that were obtained during cataract surgery. Human retinal pigment epithelial and rabbit iris pigment epithelial cells were grown on a lens capsule substrate in the presence and absence of a patterned array of inhibitory factors. RESULTS: We found that human lens capsule could be microprinted with a precision similar to that obtained on glass or synthetic polymers. Retinal pigment epithelial cells and iris pigment epithelial cells cultured onto an untreated lens capsule showed spreading and formed into fusiform-appearing cells. In contrast, cells cultured on a lens capsule with a hexagonal micropattern of growth inhibitory molecules retained an epithelioid form within the inhibitory hexagons. CONCLUSION: Inhibitory growth molecules can be micropatterned onto human lens capsule, and these micropatterns can control the organization of retinal pigment epithelial cells or iris pigment epithelial cells cultured onto the lens capsule surface. CLINICAL RELEVANCE: Microprinting on autologous human tissue may facilitate efforts to effectively organize cell cultures and transplantations for the replacement of vital ocular tissues such as the retinal pigment epithelium in age-related macular degeneration.

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