Age and brain changes are more important than IOP in glaucoma

 

Neuronal degeneration in glaucoma is characterized by early distal transport loss and damage to axonal pathology.

Mouse experiments have shown that the site of termination of retinal ganglion cell (RGC) axons in the superior colliculus (SC) shows reduced active transport. This follows a retinotopic pattern resembling glaucomatous vision loss.

Distal transport loss appears early, where RGC axons terminate in the SC. Subsequently, the deficits progress to more anterior RGC brain targets, including the optic tract and nerve, and finally to the retina, where active uptake eventually fails.

The deprivation of trophic factors due to compromised axonal integrity and transport is integral to the neurodegenerative process.

Downstream apoptotic mechanisms contribute late in glaucoma, and axonal pathology precedes somatic degeneration.

Acute glaucoma models have also demonstrated that RGC targets in the brain atrophy associated with the loss of recipient neurons.

The DBA/2 mouse glaucoma model has shown that the loss of markers (labels) in the SC do not correlate with the IOP. It is seen that the older the mouse, the more the neural deficit in the brain.

According to this research, IOP cannot predict a deficit, but aging can influence the likelihood of one for a given IOP.

REFERENCE:

Crish SD, Sappington RM, Inman DM, Horner PJ, Calkins DJ. Distal axonopathy with structural persistence in glaucomatous neurodegeneration. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5196-201. doi: 10.1073/pnas.0913141107. Epub 2010 Mar 1. PMID: 20194762; PMCID: PMC2841892.