Article The Cell and Molecular Biology of Glaucoma: Biomechanical Fa...

I hope this could be useful. I'll follow with interest the following discussion.

Best regards.

Hi DR. Pierpaolo,

Thank you for the link.

I have read the article you sent across. This article explains how IOP elevation causes RGC death. But my concern is why not the death of amacrine cells and photoreceptors

Current view on Glaucoma is an optic neuropathy and apoptosis of ganglion cells. Pressure independant mechanisms are discussed in the enclosed paper

There are two established facts in glaucoma: First, the elevated intraocular pressure (IOP) is definitively the cause of glaucoma. Secondly, the NFs are always being destroyed is an orderly tandem fashion, from peripheral to central - a feat which couldn’t be accomplished by the direct action of elevated IOP on the RGCs or their axons or in fact by any biological action. Period.

This is the puzzling mystery of glaucoma.

If the orderly and predictable loss of NFs was not occurring, we wouldn’t be doing perimetry in glaucoma as the results would be erratic and visual fields results useless. If glaucoma is a neurodegenerative disease then please explain: why one million or so RGCs always being destroyed in a orderly sequence - and never randomly ? If any glaucoma theory or factor does not give also the reason for the orderly loss of nerve fibers- will be of no value and will be immediately discarded.

In my opinion, glaucoma is a neurodegenerative disease.

I discovered a paradigm called RE-PERG® that detect RGC performance in response to a visual stress signal. Respect to the normal subject, in the glaucoma patient I found a different performance of RGC since at early stage. This is the dysfunction that precedes the apoptosis that we see as visual field loss, RNFL thinning, amplitude reduction of the common perg.

Furthermore, I found that RE-PERG® can be useful for the identification of early stage of AD, by detection of high intrinsic variability of phase in Mild Cognitive Impairment patients attributable to the magnocellular pathway dysfunction.

I think that Alzheimer disease involves the degeneration of a neuronal subpopulation in the central nervous system, included RGC.

I don't believe in the mechanical or vascular theory, even I can't answer about elevated intraocular pressure and RGC apoptosis, but I think that in glaucoma occurs primarily a dysfunction of soma RGC and consecutive apoptosis. I agree with you Muneeb, It's need understand the effect of pressure on RGC.

In order to the orderly loss of nerve fiber, may be anatomical reasons, like as in AD slow decline in memory, thinking and reasoning skills are common symptoms and not, for example, micrography of Parkinson's disease.

I agree with Syed, is very curious the orderly loss of nerve fiber!

In all the neurodegenerative disease the neurons are being destroyed randomly or haphazardly by apoptosis or some other mechanism. But in glaucoma the RGCs or their axons are being destroyed in an orderly sequence. This fact alone should keep glaucoma apart from neurodegenerative diseases. Glaucomaparadigmshift.com

These responses reflect the schools of thinking on Glaucoma: Mechanical cell death vs neurodegeneration.

Mechanical: Only RGCs have their soma in the retina and the synapse in the superior colliculus. The connecting axon traverses through the lamina cribrosa. In the presence of elevated IOP, axons can get mechanically damaged at he level of the lamina (In a nutshell, think of kinking or stretching or pressing against the hard filaments of the lamina). Following the initial axonal injury, RGCs can die retrogradely. This explains why RGCs can be lost in well-defined sectors - this could happen when a bundle of axons going through one distinct pore (or a group of pores) of the lamina are damaged. Other cell types that do not traverse the lamina survive, because the IOP itself is likely not lethal.

Neurodegeneration: The mechanics do not explain, why there are people with RGC loss but no history of IOP or why RGC loss sometimes progresses despite IOP being controlled. So normal-pressure neurodegeneration, or change in factors that govern neuronal survival, deserves investigation.

Disclaimer: I am not a glaucoma specialist.

Dr. Alt

Your input about glaucoma is very interesting.

Did you mean glaucoma is a mechanical disease in cases of elevated IOP (HTG) but in normal IOP cases ( NTG) the glaucoma is a neurodegenerative disease ?

In both HTG & NTG the visual field defects and the course of disease are same. Can you, then, please explain: why in both HTG and NTG the nerve fibers are being destroyed in the similar way if HTG is due to mechanical injury and NTG due to neurodegeneration? Is it just a co-incidence?

If NTG is a neurodegenerative disease then why are we treating it with IOP lowering drugs?