08:16pm Saturday 22 February 2020

Chemical Approach for Treating Retinal Diseases

The National Science Foundation has awarded UIC’s multidisciplinary team a four-year, $2 million grant to conduct its work. The NSF’s Office of Emerging Frontiers in Research and Innovation approved the highly competitive award to Laxman Saggere, associate professor of mechanical and industrial engineering; David Pepperberg and Haohua Qian, respectively professor and associate professor of ophthalmology and visual sciences; and Scott Shippy, associate professor of chemistry.

While the growing incidence of age-related vision loss due to retinal degenerative diseases has spawned considerable research — and progress toward finding cures — complete vision restoration remains an elusive goal. Some efforts focus on implants that stimulate the retina electrically to restore sight.

“If we can understand the optimal delivery conditions of neurotransmitters that could efficiently trigger neuronal response, then we could engineer a chemical interface at the retina to stimulate retinal cells under photo control and potentially generate neuronal signals in the retina, even though photoreceptor cells are damaged or lost due to disease,” said Saggere.

The UIC team will study natural, or native, neurotransmitter chemicals and tethered synthetic biomolecules to learn how each can be delivered to compensate for damaged retinal cells, and what are the advantages and disadvantages of each, before they design a delivery system implant.

“Each class of neurotransmitters has advantages,” said Saggere. “Natural are biocompatible, their biochemical and physiological properties are well-known, but they’re diffusible and hard to contain at the precise stimulation sites,” he said. Synthetic biomolecules, he said, can be tethered to microscale structures or packaged for precise delivery to where they’re needed, plus they are potentially long-lasting. “But we don’t yet know the optimal conditions to attach them to engineered probes or structures, or how effective they are at producing a physiological response,” he said.

Saggere will develop microfabricated structures that can be activated at the cellular level. He will also design microfluidic dispensers to package and deliver natural neurotransmitters to retinal tissue in a controlled manner.

Pepperberg and Qian will synthesize the biomolecules and develop methods for attaching them to the engineered probes that will be presented to retinal cell receptors in a controlled environment. They will also study the electrophysical response of the neurons triggered by the neurotransmitters.

Shippy will study the release characteristics of natural neurotransmitter chemicals on retinal tissue to determine optimal amounts needed and other characteristics that will help restore sight. Experiments will be done in vitro, or outside living organisms, to develop a complete understanding of the chemistry and physiology of this proposed therapy route.

“We want to understand the biomimetic (human-engineered) way of triggering cell response so we can present the correct neurotransmitters in a controlled manner,” Saggere said. Better understanding of these mechanisms, he said, may lead to new therapies and applications for other neurological diseases, such as Parkinson’s.

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