Study Published in American Journal of Human Genetics Indicates Relationship Between ApoE Gene and Glaucoma.

Business Editors & Health/Medical Writers

ALAMEDA, Calif.--(BW HealthWire)--May 29, 2002

InSite Vision holds exclusive worldwide rights to ApoE gene

for the diagnosis and treatment of glaucoma

InSite Vision Incorporated (AMEX:ISV) announced today that a peer-reviewed manuscript published in the American Journal of Human Genetics (volume 70, pages 1575-1581) indicates a relationship between the apolipoprotein E (ApoE) gene and optic nerve and visual field damage in glaucoma patients. InSite Vision has obtained the exclusive, worldwide rights for the use of the ApoE gene in the diagnosis and therapeutic treatment of glaucoma.

The manuscript entitled, "Apolipoprotein E-promoter single-nucleotide polymorphisms affect the phenotype of primary open-angle glaucoma and demonstrate interaction with the myocilin gene," was based on a retrospective study involving 191 patients with primary open-angle glaucoma (POAG).

Results of the study indicate that a single nucleotide polymorphisms (SNP) on the promoter region of the apolipoprotein E (ApoE) gene is associated with increased optic nerve and visual field damage in glaucoma patients. The study also shows that another SNP interacts with the recently reported MYOC SNP (mt1), resulting in increased intraocular pressure (IOP) and with limited effectiveness of IOP-lowering treatments in patients with POAG. Elevation of IOP is considered to be a risk factor for damage to the optic nerve and for visual field loss in POAG. Lowering of intraocular pressure is currently the primary therapeutic strategy available for preventing degradation of the visual field of POAG.

"These findings extend and refine our previous observation of an association of MYOC.mt1 with resistance to IOP control, and they strengthen the idea that this resistance probably has a genetic basis," wrote the article's senior author Henri-Jean Garchon, MD, Ph.D. "The findings also indicate that the ApoE gene, which is associated with predisposition to neurodegenerative diseases such as Alzheimer disease, may be a candidate gene for glaucoma."

"Glaucoma is a multi-genetic disease. Besides the TIGR/MYOC gene, the recently discovered Optineurin gene and the ApoE gene, several other genes could govern the pathogenesis of the disease," said S. Kumar Chandrasekaran, Ph.D., InSite Vision's Chief Executive Officer and President. "Our goal at InSite Vision is to screen for the major glaucoma-related genes and mutations to provide the broadest applicability, from disease management, including severity and progression, to detection."

A recent paper published in the February 2002 issue of American Journal of Human Genetics indicates that CYP1B1, the gene that causes the primary congenital glaucoma, interacts with the TIGR/MYOC gene resulting in an earlier onset of POAG. InSite Vision has recently extended the licensing rights of the CYP1B1 gene from the University of Connecticut Health Center to include the diagnostic and therapeutic use of the gene for POAG.

InSite Vision is an ophthalmic products company focused on glaucoma, ocular infections and retinal diseases. InSite Vision's glaucoma activities include genomic research, using TIGR and other genes, for its diagnosis, prognosis and disease management test OcuGene, as well as ISV-205, InSite Vision's novel glaucoma therapeutic. ISV-205 uses the InSite Vision's proprietary DuraSite(R) drug-delivery technology, which also is incorporated into InSite Vision's ocular infection programs ISV-401 and ISV-403, and InSite Vision's retinal program.

This press release contains among other things certain statements of a forward-looking nature relating to future events or the future business performance of InSite Vision. Such statements entail a number of risks and uncertainties, including but not limited to, market acceptance of our products, including OcuGene; our ability to maintain and develop additional collaborations and commercial agreements with corporate partners, including with respect to OcuGene; our need for significant additional funding for our capital requirements; our reliance on third parties for the development, marketing and sale of our products; and the results of preclinical and clinical studies and determinations by the U.S. Food & Drug Administration, including those with respect to Ocugene. Reference is made to the discussion of risk factors detailed in InSite Vision's filings with the Securities and Exchange Commission, including its annual report on Form 10-K and its quarterly report on Form 10-Q for the quarter ended March 31, 2002. Any projections in this release are based on limited information currently available to InSite Vision, which is subject to change. Although any such projections and the factors influencing them will likely change, InSite Vision will not necessarily update the information, since InSite Vision may only provide guidance at certain points during the year and we assume no obligation to update any such information. Such information speaks only as of the date of this release. Actual events or results could differ materially and no reader of this release should assume later that the information provided in this release is still valid.

Note to Editors: OcuGene is written with a "small cap" G; if doing so is not possible, please use an upper case G. InSite Vision Incorporated, InSite Vision, DuraSite and OcuGene are trademarks of InSite Vision Incorporated. Other trademarks that may be mentioned in this advisory are the intellectual property of their respective owners.