Research by Krish Kizhatil, Ph.D., could lay the groundwork for identifying more effective glaucoma treatments
A new five-year grant from the National Eye Institute totaling $2,187,500 to Jackson Laboratory (JAX) Associate Research Scientist Krish Kizhatil, Ph.D., will support research into mechanisms of glaucoma, an eye disease expected to affect 80 million people by the end of the decade.
Glaucoma is a disease where a progressive, irreversible vision loss results from damage to the optic nerve. Optic nerve damage results from an increase in intraocular pressure (IOP) resulting from poor drainage of aqueous humor, the clear fluid that fills the front of the eye. A structure known as Schlemm’s canal is an important gatekeeper in the drainage process.
“Current glaucoma therapy is based on reducing elevated IOP,” Kizhatil explains, “but no current drug is able to reduce IOP very effectively, indicating the pressing need for improved therapies.” Drug development has been hampered by a limited understanding of the molecular basis of IOP elevation, he says.
To address this problem, Kizhatil focuses on determining the molecular mechanisms functioning in Schlemm’s canal inner wall that facilitates aqueous humor drainage and controls IOP. Elevated IOP likely results when these molecular pathways do not function properly. The identification of these molecular pathways thus will allow identification of new targets for a more rational approach to development of effective IOP reducing drugs.
Kizhatil works in the laboratory of JAX Professor and Howard Hughes Medical Investigator Simon W.M. John. The John lab was a pioneer in using mouse for glaucoma studies and was among the first to show that mice have a Eyeing the eyeSchlemm’s canal is critical in maintaining proper fluid flow from the eye. Researchers are trying to better understand its role in ocular health and disease.Schelmm's canal that is very similar to that in humans. In 2014 Kizhatil was the first author of a paper from the John lab which, using mice, determined that the Schlemm’s canal was a unique vessel with features common to both blood and lymphatic vessels, and described the first molecule required Schlemm’s canal’s development. For that paper, the New York Academy of Medicine awarded Kizhatil its prestigious in 2015.
Kizhatil has identified a gene that is a key regulator of lymphatic development and function is expressed in the inner wall of the Schlemm’s canal. This gene appears to control IOP. The new grant will fund his exploration of this candidate gene, which he expects to yield critical new information on the mechanisms regulating IOP, laying the groundwork for identification of more effective therapeutic targets for glaucoma.
In February 2017 the John lab reported its finding that in mice genetically predisposed to glaucoma, vitamin B3 added to drinking water is effective at Vitamin B3 prevents glaucoma, JAX researchers findNew research shows that simply adding vitamin B3 to the drinking water of mice predisposed to glaucoma can prevent the debilitating eye disease.preventing the disease .
The Jackson Laboratory is an independent, nonprofit biomedical research institution based in Bar Harbor, Maine, with a National Cancer Institute-designated Cancer Center, a facility in Sacramento, Calif., and a genomic medicine institute in Farmington, Conn. It employs 2,000 staff, and its mission is to discover precise genomic solutions for disease and empower the global biomedical community in the shared quest to improve human health.
National Eye Institute: Determining How Lymphatic Molecules Control Conventional Outflow, grant number 1R01EY028175-01