An innovative use of technology that shows promise in advancing knowledge of the causes of congenital degenerative diseases of the eye, such as retinitis pigmentosa, has been developed by SUNY Upstate Medical University researcher Peter D. Calvert, Ph.D. SUNY Upstate is believed to be only one of two centers worldwide that can perform research using this technology.
The technology allows Calvert and his colleagues to view the dynamics of proteins in living retinal cells in real time at light levels that minimally perturb them. “Retinal photoreceptor cells, being the primary detectors of light and thus principal cells of the visual system, possess billions of highly sensitive light receptors called rhodopsins which, upon absorption of photons, change the activities of the cells and the proteins within them,” said Calvert, assistant professor of ophthalmology and adjunct assistant professor of biochemistry and molecular biology. “Through our approach, we are able to view protein behavior within living retinal cells at light levels that minimally activate the receptors.”
To do this, Calvert developed a specialized multiphoton microscope that allows him to evaluate protein function in live photoreceptor cells under conditions of controlled light exposure. “The microscope allows us for the first time to directly quantify light dependant changes in protein dynamics, subcellular protein localization and the cellular signals that underlie these changes,” he said.
Calvert’s laboratory also developed a new way to analyze protein dynamics in live cells that accounts for local variations in the physical properties of the cells and the cytoplasm, which is a complex milieu that consists of everything within the cell membrane and outside the nucleus. “Combined, these new advances allow hypotheses regarding the mechanisms underlying protein localization and transport in photoreceptor and other cells of normal retinas, and in retinas possessing disease causing genetic mutations, to be directly evaluated,” he said.
Many congenital degenerative diseases in a variety of tissues are caused by genetic mutations that lead to improper transport and localization of proteins within cells. Proteins perform vital work in cells and their proper localization within cells is required for the normal structure, function, and regulation of the body’s tissues and organs. Retinitis pigmentosa, a devastating disease that causes the retina in the eye to degenerate and patients to slowly become blind, often at an early age, results from a variety of genetic mutations that cause improper localization of proteins in the light detecting, retinal rod photoreceptors.
“Understanding the molecular mechanisms underlying normal protein transport and localization, and what goes wrong with these processes in congenital disease, is paramount to understanding disease mechanisms and to the development of new therapies,” said Calvert.
To further Calvert’s studies, Research to Prevent Blindness, the world’s leading voluntary organization supporting eye research, has granted him and SUNY Upstate’s Department of Opthalmology a four‑year $200,000 Career Development Award.