Does the aqueous humor have a role in mitogen-activated protein kinase (MAPK) intracellular signaling in Glaucoma?

Abstract

Glaucoma is a common blinding disease worldwide. Glaucoma treatment today is based on reduction of aqueous humor production or increase aqueous humor drainage. By medical manipulation, the treatment goal is to reduce the main risk factor, elevated intra ocular pressure. Here we hypothesize that the aqueous humor has a role, beside oxygen and nutrient supply, in transferring signaling to the trabecular meshwork. This signaling might be delivered from the ciliary body were the aqueous humor is produced, or from the lens or the cornea. Recently in our lab we proposed that MAPKs present in the aqueous humor are a novel signal involved in glaucoma pathology. Here we show that this pathway exists at an unexpected, extracellular media. Western blot analysis of aqueous humor from congenital glaucomatic rabbits and a rat model of induced elevated intra ocular pressure (IOP) were found to express several signaling members of the MAPK family. Although these members are usually found in an intracellular environment, they can be detected at an extracellular environment, namely the aqueous humor. These signaling proteins are found also in normal eyes. Moreover the MAPK signaling proteins are found in the active phosphorylated form and in non-active form in elevated IOP animals as well as in the control, normal IOP groups. Understanding the signaling cascade, at the aqueous humor, opens a new area for treatment of glaucoma patients. By interfering with the signaling cascade, taking place at a reachable location, the anterior chamber, we will be able to manipulate these protein effects on the trabecular meshwork.