Washington: Scientists, including one of Indian origin, have discovered that a light-sensing pigment found in everything from bacteria to vertebrates can be manipulated to help improve vision in humans.
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 (GPCRs) - that sit in cell membranes and transmit external cellular cues into internal cell signalling pathways.
"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," said Sahil Gulati, from Case Western Reserve University in the US."These findings exemplify the possibility of reprogramming GPCRs into self-renewing machines that can be controlled by external cues," said Gulati.
"This biochemically induced function will be helpful in treating people with vision impairment, and opens up several avenues for more efficient GPCR-based therapeutics," he said. Researchers discovered the self-renewing mechanism in
bovine rhodopsin, which is exceptionally similar to human rhodopsin.
They then used purified proteins in their laboratory to show that their modified retinal molecule binds to bovine rhodopsin and successfully activates specific human eye
proteins in response to light. When complete, it uses thermal energy to slowly return to
its inactive form that can be repeatedly reactivated with light. The findings suggest that retinal molecules with the specific chemical structure could reversibly stimulate
rhodopsin that drives human vision.
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, researchers said. Light photons enter the eye and get absorbed by the retinal-rhodopsin complex, activating a cascade of downstream signals that constitute vision. 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, researchers said.
However, this transformation is a one-way ticket and requires an army of specialised proteins to convert all-trans-retinal back to 11-cis-retinal."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 Gulati.The study was published in the journal Proceedings of the National Academy of Sciences.
