A light-sensing pigment found in everything from bacteria to vertebrates can be biochemically manipulated to reset itself, an important therapeutic advantage, according to new research out of Case Western Reserve University School of Medicine. In a study just released from the Proceedings of the National Academy of Sciences, researchers successfully used a modified form of vitamin A, called locked retinal, to induce the recycling mechanism and engage proteins central to human vision. The targeted proteins include light-sensing rhodopsin, which belongs to a family of proteins--G protein-coupled receptors, or GPCRs--that sit in cell membranes and transmit external cellular cues into internal cell signaling pathways. The discovery opens a new therapeutic opportunity for modified retinals that help improve vision, and offers a major improvement over current therapeutics designed to perturb cell signaling in the eye.
"Our study demonstrates a complete transition from a one-way activation of a GPCR into a self-renewing, recycling activation mechanism by the mere addition of a cyclohexyl chemical group to the retinal. These findings exemplify the possibility of reprogramming GPCRs into self-renewing machines that can be controlled by external cues. This biochemically induced function will be helpful in treating people with vision impairment, and opens up several avenues for more efficient GPCR-based therapeutics," said Sahil Gulati, first author of the study and graduate student in the department of pharmacology at Case Western Reserve University School of Medicine. Krzysztof Palczewski PhD, professor and chair of the department, served as senior author for the study.
The discovery digs into the biochemistry of vision and why the chemical configuration of the retinal is critical for humans to perceive light. Humans see with the help of an extremely sensitive protein in the back of the eye called rhodopsin, which attaches to a retinal molecule to sense light. Light photons enter the eye and get absorbed by the retinal-rhodopsin complex, activating a cascade of downstream signals that constitute vision. Importantly, the retinal awaits light photons while maintaining a particular chemical configuration--11-cis retinal--and transforms into a second configuration--all-trans retinal--after it absorbs a light photon. But this transformation is a one-way ticket, and requires an army of specialized proteins to convert all-trans-retinal back to 11-cis-retinal. Inherited mutations in any of these specialized proteins can cause retinal degenerative diseases. Researchers who want to treat such diseases must repair or bypass the mutated proteins to maintain this retinal conversion in humans.
Read full article at: http://www.news-medical.net/news/20170406/Study-shows-how-chemical-modification-in-the-retinal-can-improve-vision.aspx
Related article at: Biochemistry Help Online
"Our study demonstrates a complete transition from a one-way activation of a GPCR into a self-renewing, recycling activation mechanism by the mere addition of a cyclohexyl chemical group to the retinal. These findings exemplify the possibility of reprogramming GPCRs into self-renewing machines that can be controlled by external cues. This biochemically induced function will be helpful in treating people with vision impairment, and opens up several avenues for more efficient GPCR-based therapeutics," said Sahil Gulati, first author of the study and graduate student in the department of pharmacology at Case Western Reserve University School of Medicine. Krzysztof Palczewski PhD, professor and chair of the department, served as senior author for the study.
The discovery digs into the biochemistry of vision and why the chemical configuration of the retinal is critical for humans to perceive light. Humans see with the help of an extremely sensitive protein in the back of the eye called rhodopsin, which attaches to a retinal molecule to sense light. Light photons enter the eye and get absorbed by the retinal-rhodopsin complex, activating a cascade of downstream signals that constitute vision. Importantly, the retinal awaits light photons while maintaining a particular chemical configuration--11-cis retinal--and transforms into a second configuration--all-trans retinal--after it absorbs a light photon. But this transformation is a one-way ticket, and requires an army of specialized proteins to convert all-trans-retinal back to 11-cis-retinal. Inherited mutations in any of these specialized proteins can cause retinal degenerative diseases. Researchers who want to treat such diseases must repair or bypass the mutated proteins to maintain this retinal conversion in humans.
Read full article at: http://www.news-medical.net/news/20170406/Study-shows-how-chemical-modification-in-the-retinal-can-improve-vision.aspx
Related article at: Biochemistry Help Online
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