SC CTSI-Supported Researchers make important discovery on Ameliorate Dry Eye treatment

Researchers find natural protein seals ocular surface and offers promise to ameliorate dry eye.

October 07, 2015

Note: Researchers Elizabeth Fini, Ph.D, and Aditi Bauskar received support from the SC CTSI Biostatistics program for their study investigating the role of clusterin in protecting the ocular surface barrier.

Millions of people suffer from dry eye conditions brought on by causes such as aging, eye surgery or environmental exposure. Dry eye represents one of the most common conditions seen by eye care practitioners. It significantly impacts patients’ quality of life and if left untreated, more severe cases may result in vision loss due to corneal scarring.

Recent research by Keck Medicine of the University of Southern California (USC) scientists, published in PLOS ONE, suggests a new approach to treating dry eye. Using an experimental mouse model, the researchers demonstrated for the first time that the natural tear protein clusterin seals the ocular surface barrier, while also protecting against further damage.

Findings show that clusterin blocks uptake of fluorescein dye, a clinical test used to diagnose dry eye, according to senior and corresponding author Shinwu Jeong, Ph.D., assistant professor of research ophthalmology in the Institute for Genetic Medicine at the Keck School of Medicine of USC.  “It is well known that clusterin protects cells and proteins”, he said.  “A problem in dry eye appears to be that natural clusterin is depleted. We predicted that adding it back would be beneficial, however the novel mechanism of sealing was unexpected.”

The researchers studied the ocular surface barrier rather than upstream effects of tear production; tear chemistry and inflammation that contribute to dry eye conditions.

“We are the first to report functions for this protein in dry eye and shed some light on its potential use for ophthalmology treatments,” said Aditi Bauskar, a Ph.D. graduate student in USC’s medical biology program, and lead author on the paper. “Our pre-clinical results are very promising and make a strong case to use clusterin as a biological drug to prevent or treat not only dry eye, but also other corneal disorders involving damage to the ocular surface barrier.”

Currently there are no drugs on the market addressing ocular surface barrier disruption.  This work is the basis of several patent applications with USC Stevens Center for Innovation, one that has just issued. Research was conducted in the lab of M. Elizabeth Fini, Ph.D., director of the USC Institute for Genetic Medicine and professor of cell & neurobiology and ophthalmology. Other USC co-authors include faculty members Wendy J. Mack (preventive medicine and SC-CTSI), Martin Heur (ophthalmology) and Janet Moradian-Oldak (Ostrow School of Dentistry).

Funding was provided by the James H. Zumberge Faculty Research & Innovation Fund, National Institutes of Health grants, Research to Prevent Blindness, University of Southern California and the Keck School of Medicine of USC.

Bauskar A, Mack WJ, Mauris J, Argüeso P, Heur M, Nagel BA, Kolar GR, Gleave ME, Nakamura T, Kinoshita S, Moradian-Oldak J, Panjwani N, Pflugfelder SC, Wilson MR, Fini ME, Jeong S (2015) Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye. PLoS ONE 10(9): e0138958. doi:10.1371/journal.pone.0138958

NIH Funding Acknowledgment: Important - All publications resulting from the utilization of SC CTSI resources are required to credit the SC CTSI grant by including the NIH funding acknowledgment and must comply with the NIH Public Access Policy.