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New research points to novel therapy for glaucoma

  November, 9 2005 0:39
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Glaucoma is the second leading cause of blindness. It is estimated that over 3 million Americans have glaucoma but only half of those know they have it. Elevated pressure in the eye is a risk factor, but even people with normal pressure can lose vision to glaucoma. Approximately 120,000 people are blind from glaucoma, accounting for 9% to 12% of all cases of blindness in the U.S. About 2% of the population ages 40-50 and 8% over 70 have elevated intra-ocular pressure (IOP) which is thought to lead to blindness through pressure-based damage to the head of the optic nerve. In normal people, the IOP is regulated through control of the aqueous humor by two outflow pathways; the conventional outflow pathway (controls about 80% of the outflow) and the uveoscleral outflow (the other 20%).

In conventional outflow, the aqueous humor passes through a tissue just under the iris called the trabecular meshwork (TM). The ‘drain-ability’ of the TM was thought be controlled by the neighboring ciliary body; a smooth muscle-like tissue that contracts and dilates the TM – increasing outflow. The TM then drains the aqueous into a specialized structure called Schlemm’s canal that, in turn, empties into the nasal vein and enters the blood system. In the glaucomatous eye, this drainage system can become blocked causing a progressive increase in IOP as aqueous humor production continues but drainage reduces.

Previously, the trabecular meshwork was thought of as a passive tissue under the control of the neighboring ciliary body but in a recent paper from Alvarado and colleagues published in the British Journal of Ophthalmology, the paradigm is turned on its head.

In this elegant study, the authors use a laser on isolated trabecular meshwork endothelial cells to mirror the effect of a laser trabeculoplasty – a popular glaucoma treatment thought to increase outflow through TM cytokine release. Once treated with the laser, the tissue culture media was collected and introduced onto isolated Schlemm’s canal endothelial cells (SCEs) and the conductivity (a measure of fluid movement) of SCEs measured. The effect of this was striking. The SCE cells increased their conductivity responses four-fold compared to controls suggesting that the TM-conditioned media induced an increased drainage. Using microarrays, the authors showed a staggering differential expression of 1570-genes in SCEs as a function of TM-conditioned media addition. Using standard ELISAs the authors identified four cytokines, IL-1alpha, IL-1beta, Il-8 and TNFalpha secreted by laser treatment from trabecular meshwork endothelium. Using purified versions of these cytokines on plated SCE cultures the authors were able to partially repeat the increase conductivity seen with the TM media.

This study shows, for the first time an active and direct effect for the trabecular meshwork tissue in the regulation of IOP and highlights possible targets for pharmacological intervention in the form of cytokines that mediate this IOP regulation and their effect upon the Schlemm’s canal endothelium

Message posted by: Simon Chandler

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