Role of receptors in the trabecular meshwork of the eye as targeted to the development of antiglaucoma therapy

The major pathway for the outflow of aqueous humor from the anterior chamber of the eye is the trabecular meshwork/Schlemm's canal system. The meshwork is composed of connective tissue beams that are ensheathed by trabecular cells; these cells derive their nutrition from the aqueous humor and thus are uniquely susceptible to morphologic and biochemical regulation by bioactive substances that are present or released in this fluid and to pharmacologic agents that are targeted to act on the tissue. The receptors that have been detected on trabecular cells include those for growth modulatory peptides (bFGF, TGF‐βI, transferrin, IGF‐1, and EGF), epinephrine, dopamine, glucocorticoids, benzodiazepines, prostanoids, biogenic amines, the Fc portion of IgGs, and probably those for molecules of the extracellular matrix (integrins). Selective up‐ or down‐regulation of the receptors on the trabecular cells would facilitate an effective control of the intraocular pressure in diseased conditions of the eye. We discuss the prospects and hurdles in the utilization of receptor targeting as a therapeutic modality for trabecular cell regeneration in glaucoma as well as for pharmacologic trabeculectomy and as a treatment for hypotony after glaucoma filtration surgery. We believe that regulation of receptor expression is a novel method for the development of new antiglaucoma agents and for minimizing the side effects of drugs that are administered topically and systemically for the control of the intraocular pressure. © 1992 Wiley‐Liss, Inc.