Molecular Mechanisms Of Glaucoma

National Eye Institute

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Abstract

It is now well established that a genetic component may contribute to glaucoma, and several glaucoma-associated genes have been identified. The first identified and the most studied gene is Myocilin, which is heavily expressed in and secreted by the trabecular meshwork, one of the key components of the eye aqueous humor outflow system. The myocilin protein belongs to a family of glycosylated proteins containing a C-terminal olfactomedin domain. Dominant mutations in Myocilin are found in 3-4% of patients with primary open angle glaucoma and most of these glaucoma-causing mutations are located in the olfactomedin domain. The function of wild-type Myocilin is not clear. We continue to study function of myocilin and two related olfactomedin domain-containing proteins, olfactomedin 1 and optimedin. We demonstrated that these three proteins are able to induce changes in cell actin cytoskeleton similar to those induced by wnt proteins. Subsequent analysis indicated that olfactomedin 1 and myocilin may serve as modulators of the non-canonical wnt-signaling pathway and interact with several key component of wnt-signaling pathway including Wif1 and sFRP1. These data add Myocilin and olfactomedin 1 to the list of the proteins involved in wnt signaling. We suggest that Myocilin is involved in the regulation of intraocular pressure through alteration of contractility of the trabecular meshwork.