PI: Laxman Saggere, Mechanical and Industrial Engineering, University of Illinois at Chicago (UIC)
Intellectual Merit
Retinal degenerative diseases such as age-related macular degeneration (AMD) affect over 10 million people in the US alone, causing a significant decline in the quality of their lives. Currently available therapies are at best only somewhat effective. Over the last two decades, several groups around the world have been pursuing the development of a retinal prosthesis, with the goal of providing a restorative aid for patients affected by retinal diseases due to photoreceptor degeneration. Nearly all of the current retinal prosthesis developments rely on the principle of stimulating the retina electrically, which is conceptually simple; however, a number of challenges still remain to be overcome in this approach and fully functional, long-lasting devices are not on the immediate horizon. On the other hand, a widely occurring mechanism of intercellular communication in the normally functioning retina as well as elsewhere in the nervous system is the chemical synapse. Inspired by the nature's complex mechanism of transducing visual information into chemical signals via the chemical synapse, the applicants envision an unconventional, but rational, approach to restore the lost functionality of photoreceptors: a light modulated chemical interface at the retina.
Toward this long-term vision of a chemically based retinal implant, the proposed project seeks to understand how the retina and retinal neurons respond physiologically to controlled focal presentation of chemical stimuli in vitro so that a general engineering framework for developing a prosthetic system based on the functionality of the diseased neurons can be further explored. There exist two distinct classes of chemicals, viz. native neurotransmitters and tethered synthetic biomolecules, that are promising as transmitters, and each offers certain unique advantages. Therefore, in this project, they propose to investigate the efficacy and feasibility of eliciting physiological responses of retinal neurons when focally stimulated by both types of chemicals delivered by means of specially engineered micro- and nanoscale delivery devices.
This novel approach is fundamentally different from the more common approach of electrically stimulating retinal neurons, and distinct from chemical-based strategies recently proposed by other groups. Thus, the main intellectual merit of this proposal lies in generating new scientific and technical knowledge that could be transformative to the development of a biomimetic retinal implant to restore lost or damaged retinal function. Ultimately, if successful, this research could lead to a new paradigm and breakthroughs in retinal prostheses.
Broader Impacts
The proposed project, if successful, could break new ground in the area of visual prosthesis and someday help provide vision perception to millions of people affected by retinal degenerative diseases. The devastating complications associated with vision loss, and the progressive aging of the US population with a corresponding increased incidence of AMD in otherwise healthy individuals, emphasize an urgent national need to develop effective prostheses and therapies for retinal degenerative diseases. Beyond the impact on vision health, this research could also lead to other novel drug delivery strategies and biomimetic therapies for treating a variety of neurological disorders such as Parkinson's.
The interdisciplinary collaboration of researchers with a diverse expertise in this project provides a unique opportunity and framework for interdisciplinary education and training of secondary school through postdoctoral students at the frontiers of engineering, neuroscience, and medicine. Four graduate students and one postdoctoral student will undertake interdisciplinary research addressing the tasks involved in this project in the investigators' labs across three different colleges at UIC. Several educational activities integrated with the proposed research including undergraduate research and outreach will be implemented.
