This is really a question that has plagued everyone involved in glaucoma research. According to the most accepted theory in patients with open-angle glaucoma, there is increased resistance to aqueous outflow through the trabecular meshwork. This leads to increased Intraocular pressure–which in turn induces stress and strain on the lamina cribrosa with consequent mechanical axonal damage and disruption of axonal transport in the retinal nerve fiber layer.

Since the resistance in the TM has never been actually measured or seen genetics were looked at for the answer. The first relevant gene at the GLC1A locus is MYOC, which encodes the protein myocilin. Carriers of disease-associated mutations develop the glaucoma phenotype in an estimated 90% of the cases. It appears that mutations alter the myocilin protein in a way that disrupts normal regulation of intraocular pressure. Disease-associated forms of myocilin interfere with protein trafficking and result in intracellular accumulation of misfolded protein. Failure to adequately secrete the protein is thought to somehow cause the intraocular pressure to increase. This simply is theoretical and no one has actually quantified these proteins.

Another is the CAV1/CAV2 (HGNC:1527/HGNC: 1528) locus on 7q34 .These genes encode proteins (caveolins) involved in the generation and function of caveola, which are invaginations of the cell membrane involved in cell signaling and endocytosis. This finding again is to quantified in glaucoma patients.

Thus what you are looking at is a field that has lot of potential for research. We still are chasing IOP reduction as the only measurable intervention that stems the damage of glaucoma, its high time someone actually finds the root cause that hampers the aqueous homeostasis, which subsequently cascades into glaucoma and its sequelae.

More avaialble from: 10.1111/ceo.12013

10.1001/jama.2014.3192

This is really a question that has plagued everyone involved in glaucoma research. According to the most accepted theory in patients with open-angle glaucoma, there is increased resistance to aqueous outflow through the trabecular meshwork. This leads to increased Intraocular pressure–which in turn induces stress and strain on the lamina cribrosa with consequent mechanical axonal damage and disruption of axonal transport in the retinal nerve fiber layer.

Since the resistance in the TM has never been actually measured or seen genetics were looked at for the answer. The first relevant gene at the GLC1A locus is MYOC, which encodes the protein myocilin. Carriers of disease-associated mutations develop the glaucoma phenotype in an estimated 90% of the cases. It appears that mutations alter the myocilin protein in a way that disrupts normal regulation of intraocular pressure. Disease-associated forms of myocilin interfere with protein trafficking and result in intracellular accumulation of misfolded protein. Failure to adequately secrete the protein is thought to somehow cause the intraocular pressure to increase. This simply is theoretical and no one has actually quantified these proteins.

Another is the CAV1/CAV2 (HGNC:1527/HGNC: 1528) locus on 7q34 .These genes encode proteins (caveolins) involved in the generation and function of caveola, which are invaginations of the cell membrane involved in cell signaling and endocytosis. This finding again is to quantified in glaucoma patients.

Thus what you are looking at is a field that has lot of potential for research. We still are chasing IOP reduction as the only measurable intervention that stems the damage of glaucoma, its high time someone actually finds the root cause that hampers the aqueous homeostasis, which subsequently cascades into glaucoma and its sequelae.

More avaialble from: 10.1111/ceo.12013

10.1001/jama.2014.3192

Pigment accummulation in the anterior chamber angle causes resistance to aqueous humor outflow. The latest approach is Selective Laser Trabeculoplasty which destroys pigment and is repeatable noninvasive procedures.Years latter SLT could be a first-line therapy for POAG

Mostly, Anatomical structure of TM changes and rest pigment/ lens matter/ FB blocked the TM, resulting in High IOP.

Open angle glaucoma is actually a disease of theories consisting of mechanical, vascular and others. Thickening and sclerosis of trabecullar meshwork is believed to play an important role in icreasing resistance to aqueous outflow.

I don't think it is a molecule. IT is the beams of the trabecular meshwork which are composed of many moieties which lead to resistance to the aqueous outflow. There are some genes/protein involved. The one that has been best characterized in this regard is MYOC (TIGR). Its upregulation leads to thickening of trabecular meshwork beams and hence reduction in pore size and consequent elevation in IOP. Additional mechanisms are mitochondrial oxidative damage, CYP1B1 mutatios etc.

However, cellular debris gets accumulated in valves and glaucoma implants. that is the main reason of their failure.