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Research

Retina comprises several well-characterized type of neurons and synapses which are organized in discrete layers. Visual information flows in retina primarily from photoreceptors → bipolar cells → retinal ganglion cells (RGCs), and eventually to the brain. This transmission is disrupted in neurodegenerative diseases such as Retinitis Pigmentosa and Age-Related Macular Degeneration where typically photoreceptors are degenerated but the RGCs are relatively preserved. In another set of diseases like Diabetes, Glaucoma and Multiple Sclerosis, retinal neurons, particularly ganglion cells undergo secondary degeneration and cell death. There is no effective treatment available to restore the function of retinal neurons in these diseases.

One promising approach to treat these diseases is to replace the degenerated photoreceptors with a prosthetic device. Retinal prosthesis is a complex electronic gadget surgically implanted in the eye to stimulate the surviving retinal neurons through an array of miniature electrodes. An ideal prosthesis would comprise an image sensor/transducer to capture and convert the visual information into spatiotemporal electrical signals, and an array of electrodes to transmit the electrical signals to the surviving retinal neurons and hence to the brain. Several research groups have made significant progress in improving the quality of retinal prostheses and their surgical implantation, but the clinical success has been limited.

Implantation of a prosthetic device in a blind patient typically produces only a subjective visual sensation of spots of light, called phosphenes. One fundamental issue is that our understanding of how exactly the first and second order retinal neurons transmit their signal to RGCs, and how RGCs encode the signal for transmission to the brain remains inadequate.Our lab is interested in unraveling how exactly a ganglion cell receives visual information as electrochemical signals in space and time, and how it encodes them for transmission to the brain. We employ methods, such as electrophysiology, computer programming, immunocytochemistry, pharmacology, and behavioral analyses in normal and transgenic animal models.

Another treatment approach is to transplant stem cells of various origins. The transplanted stem cells have been shown by several labs to differentiate into retinal cells which integrate with the host retinal neurons. However, the evidence that they make specific synaptic connections and respond to their natural stimulus has been lacking. For example, the transplanted cells that differentiate into putative photoreceptors should not only connect to the postsynaptic bipolar cells but also respond to light. In our lab we transplant stem cells into an animal model and study their migration, differentiation, synaptic integration, and functioning, using immunocytochemistry, tissue culture, electrophysiology and behavioral analysis.

 

   
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