Plasminogen activator inhibitor type 2 may play role in infection and dry eye

May 17 2006

Plasminogen Activator Inhibitor Type 2 (PAI-2), a protein found in various cell types including the skin, has been discovered in the tissue covering the eye and may have future clinical implications in various pathologies of the ocular surface such as eye infection or dry eye, according to researchers at the University of Pennsylvania and Temple University.

The researchers, led by Mina Massaro-Giordano, M.D., of the University of Pennsylvania's Scheie Eye Institute, and Marcella Macaluso, Ph.D., of the Sbarro Institute for Cancer Research at Temple University, published their study,

"Cytoplasmic and nuclear interaction between Rb family proteins and PAI-2: a physiological crosstalk in human corneal and conjunctival epithelial cells," in Cell Death and Differentiation (www.nature.com/cdd).

They recently presented their findings at the annual meeting of the Association of Research in Vision and Ophthalmology (ARVO) in Florida, which was attended by over 10,000 researchers.

PAI-2, in either extracellular or secreted form, is a multifunctional protein that plays a role in cell differentiation, in prevention of programmed cell death, in the regulation of cell proliferation, in the inhibition of microbial proteinases and in the protection against stromal degradation.

High levels of the PAI-2 protein are associated with a good prognosis in breast cancer, small cell lung, ovarian cancer, and inhibition of metastasis. PAI-2 also plays a role in inflammation on the surface of the eye.

In their study, the Penn and Temple researchers demonstrate for the first time an interaction between PAI-2 and the tumor suppressing gene Rb2/p130 in the nucleus of the epithelial cells in the cornea and conjunctiva.

According to the researchers, this interaction with Rb2/p130 and chromatin modeling enzymes may affect how PAI-2 is expressed.

"There is a different expression of the protein between the epithelium of the cornea and conjunctiva cells," says Massaro-Giordano, an assistant professor of ophthalmology, cataract and refractive surgery at Scheie. "This may help us understand the molecular mechanisms that dictate the different expression profiles of PAI-2 in human corneal and conjunctival epithelial cells."