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Research uncovers IOP regulation in glaucoma

San Francisco—How aqueous humor responds to mechanical stimuli at the cellular level (mechanosensing) affects the regulation of IOP through cells converting those stimuli into chemical activity (mechanotransduction), according to an article published April 4 in PLoS ONE, an open-access, peer-reviewed, scientific journal produced by the Public Library of Science.

“With elevated IOP being the primary modifiable risk factor affecting the development and progression of glaucoma, this advancement opens up potential avenues for effective and innovative manipulation of the pathway of aqueous outflow using mechanosensors and mechanotransducers,” said Richard K. Lee, MD, PhD, an associate professor of ophthalmology at Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine, Miami. “In turn, it could lead to meaningful intervention strategies.”

The new insight into the regulation of IOP in glaucoma resulted from a 6-year collaboration between Dr. Lee and Sanjoy Bhattacharya, MTech, PhD, also an associate professor of ophthalmology at the institution.

Drs. Lee and Bhattacharya also found that mechanosensing of fluid flow is transduced, or converted into chemical signals, by TREK-1 mechanotransducers on the cell surface. TREK-1 is a protein in the trabecular meshwork (TM), but how it affects IOP previously was not known.

At the center of their discovery is the protein cochlin, found in the TM 7 years ago using highly sensitive mass spectrometry. Missing was an understanding of how cochlin works in mechanosensing. Drs. Lee and Bhattacharya’s research demonstrated that TREK-1 functions in conjunction with cochlin to regulate IOP. Further, Drs. Lee and Bhattacharya determined that aberrant levels of secreted cochlin disrupt aqueous outflow, thus allowing for a rise in IOP.

“Fluctuations of IOP can alter cells of the TM,” Dr. Bhattacharya said. “This results in dysfunction of aqueous flow.”

Currently, more than 2 million known proteins and 46,000 lipids can be tested to determine their effect on IOP, he added.

To read the article, visit Funding for the research came from two National Institutes of Health grants totaling $3.4 million.

Using advanced mass spectrometry techniques, Drs. Lee and Bhattacharya next hope to uncover endogenous and exogenous molecules that regulate aqueous humor outflow by modulating mechanosensors and mechanotransducers.

For more articles in this issue of Ophthalmology Times eReport, click here.

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