Studies Link Glaucoma Gene Product To Non-Hereditary Glaucoma

May 14, 1997

InSite Vision Developing Products Based On Findings

NOTE: A media conference call with scientists in the field of ophthalmology who have demonstrated that the TIGR gene and its product, the TIGR protein, have a central role in non-hereditary forms of the disease will be held on Thursday, May 8 at 11:30 am PACIFIC TIME.

ALAMEDA, CA, May 14, 1997 - InSite Vision Incorporated (Nasdaq: INSV) today announced that the Company's collaborators at the University of California, San Francisco (UCSF) have demonstrated that the TIGR gene, a defect of which was recently identified as a cause of glaucoma, also has a central role in non-hereditary forms of the disease. These findings may lead to the development of novel approaches to glaucoma diagnostics, treatment and prevention. InSite Vision is developing genetic screening tools for glaucoma based on the TIGR technology as well as ISV-205, a related glaucoma treatment utilizing the Company's DuraSite( ophthalmic drug delivery technology. The UCSF research will be published in the May issue of the journal Ophthalmologica. Additional data was presented yesterday at an international vision research meeting in Ft. Lauderdale, Florida.

Earlier this year, the UCSF researchers joined with other geneticists and ophthalmologists in the publication in Science of a defect in the TIGR gene that causes glaucoma. This important finding may make it possible to identify individuals who inherit the gene defect so that they can be followed carefully and given therapies to prevent vision loss. The new work described by the UCSF researchers and colleagues builds on the gene discovered with a series of experiments using the TIGR protein, a product of the TIGR gene that is produced in ocular trabecular meshwork (TM) cells. In the studies, the presence of the TIGR protein blocked the outflow of fluid through TM cells, which may lead to an elevation of intraocular pressure (IOP), a hallmark of glaucoma. Further, the researchers found that exposure of TM cells to steroid drugs known to cause elevated IOP resulted in increased TIGR protein production, as did exposure of the cells to oxidative stress, a mechanism thought to be involved in primary open-angle glaucoma, the form of the disease most associated with the aging process. The scientists then confirmed their findings by showing a significant increase in the TIGR protein in the trabecular meshwork of patients with primary open-angle glaucoma and in trabecular meshwork exposed to long term steroid treatment.

Finally, the researchers showed the TM cells could be prevented from producing the TIGR protein in response to steroids or oxidative stress by ISV-205, a high-dose DuraSite-based formulation of a non-steroidal anti-inflammatory drug. ISV-205 has been evaluated in a Phase I clinical safety study in healthy volunteers and is expected to enter Phase II testing later this year.

"A new understanding of how and why glaucoma occurs is developing as a result of this research," said Richard Lewis, M.D., clinical professor of ophthalmology at the University of California, Davis. "I'm very hopeful that this information will accelerate the development of new diagnostic tools and treatments to prevent irreversible vision loss and blindness due to glaucoma."

"We are pleased to be working on two exciting approaches to the management of glaucoma," said Kumar Chandrasekaran, Ph.D., InSite Vision's Chairman and Chief Executive Officer. "With ISV-205, we are developing a product candidate designed to attack glaucoma by preventing TIGR production in TM cells. If successful, ISV-205 could be used to treat glaucoma as well as to prevent IOP elevation when steroids are given to reduce inflammation after eye surgery. We also are using the TIGR gene defect as well as gene defects associated with other forms of glaucoma to develop diagnostic and prognostic kits designed to identify those with a hereditary predisposition to the disease."

The paper, "Cellular Pharmacology and Molecular Biology of the Trabecular Meshwork Inducible Gluccorticoid Response (TIGR) Gene Product," was authored by UCSF researchers Jon Polansky and Thai Nguyen along with their primary collaborators at the Mayo Clinic and the University of Erlangen-Nuernberg, Germany.


Often referred to as "the silent thief of sight," glaucoma has afflicted an estimated two to four million Americans. The numbers vary since so many victims go undiagnosed. Glaucoma is a disorder characterized by increased intraocular pressure that may cause impaired vision, ranging from slight sight loss to complete blindness.

InSite Vision is an ophthalmic pharmaceutical company focused on the development of improved and novel eye medications based on its proprietary DuraSite( eyedrop-based delivery system, and on the development of genetically-based tools for the diagnosis and prognosis of glaucoma. DuraSite-based products are designed to permit the gradual release of drug into the eye over a period of hours, thereby overcoming various treatment problems common with conventional ophthalmic drug delivery.

This press release contains certain forward-looking statements reflecting InSite Vision Incorporation's current expectations. These statements are made under the "safe harbor" provisions of Section 27A of the Securities Act of 1933 and Section 21A of the Securities Exchange Act of 1934. Investors are cautioned that all forward-looking statements involve risks and uncertainties which may cause actual results to differ from those currently anticipated by InSite Vision, including, without limitation: risks inherent in developing a genetic discovery into a commercially viable diagnostic product, which include issues of manufacturability, proving the validity of diagnostic, preclinical and clinical studies and obtaining, if required, approvals from the U.S. Food and Drug Administration; changes in demand for the Company's products; rapidly changing markets and advancing technologies; keen competitive pressures; and those matters set forth under the heading "Risk Factors" listed from time to time in the Company's SEC filings. Investors are encouraged to review InSite Vision's Quarterly Report, Form 10-Q for the quarter ended March 31, 1997, filed with the SEC, for a more complete discussion of factors that could cause InSite Vision's results to differ from current expectations.



Media conference call with scientists in the field of ophthalmology who have demonstrated that the TIGR gene and its product, the TIGR protein, have a central role in non-hereditary forms of the disease.

The findings of the study are being published in the May issue of the journal Ophthalmologica, and additional data is being presented at the annual Association for Research in Vision and Ophthalmology meeting in Fort Lauderdale, Florida, this month.

Discovery of the glaucoma gene is recent, and the cause of glaucoma - a disease afflicting approximately two to four million Americans - is still unknown. This important finding may make it possible to devise novel treatments and diagnostic tools for glaucoma - based on the new understanding of the pathogenesis of the disease.

Thursday, May 8, 11:30 A.M. Pacific Time

Journalist interested in participating in media conference: call toll free 1 800 390 5048 and give confirmation no.679453.

For further information contact: Barbara Heineback at Russell-Welsh, Inc. (U.S.A.) (415) 312-0700, ext. 21

Russell-Welsh Public Relations

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