What is functional genomics teaching us about intraocular pressure regulation and glaucoma?

Glaucoma is a complex disease characterized by the degeneration of the optic nerve and subsequent loss of vision. The disease affects a large number of people, especially those among the older population. The causes leading to the development of glaucoma can be the result of the dysfunction of several tissues. The major risk for glaucoma is elevated intraocular pressure which is the consequence of an improper regulation of aqueous humor outflow in the anterior segment of the eye (ciliary body and trabecular meshwork). Elevated pressure in turn, affects the posterior segment by exerting mechanical strain on the optic nerve and provoking deformation, distortion of axonal flow and death of the nerve cells (lamina cribrosa and retinal ganglion cells). The function of any given tissue is governed by the regulation of expression of its genes. Functional genomics offers an invaluable tool to identify the molecular differences affecting the cells under conditions associated with glaucoma. In this chapter, we have reviewed such changes. Because of the wide scope of the project, we have briefly reviewed studies in all tissues and then concentrated in those conducted on the trabecular meshwork, the keeper of outflow resistance. We have analyzed and correlated our internal data with that of other laboratories, and built a molecular signature for trabecular meshwork pathophysiology. We identified and present a set of 40 genes. These include new genes involved in known trabecular meshwork physiology as well as genes representative of new processes and mechanisms. As the functional genomics studies on RNA, proteins, protein modifications and activities continues this list will be further edited. As of today, this signature provides the opening of a small window into the global mechanisms governing the development of glaucoma.