Glaucoma comprises a group of optic neuropathies by progressive degeneration of RGCs; resulting in characteristic changes in the ONH and RNFL, and VF defects. The biological basis of glaucoma is poorly understood, and the factors contributing to its progression have not been fully characterized. Diagnosis of glaucoma is by a combination of identifying characteristic changes of the RGCs and ONH, functional testing such as VFs, and structural imaging of the retina.
Sometimes, however, OCT analysis and the VF test are infeasible because of refractive medium opacity conditions. More importantly, as many as 30 to 50% of RGCs may lose before VF defects are detectable in clinical examination. Early diagnosis and treatment of glaucoma are key to preventing vision loss. To date, no biochemistry indexes have used for diagnosis or evaluation of the severity of axonal injury or axonopathy.
The glaucoma pathogenesis
Axonal transport deficits or axonopathy is a component of early glaucoma pathogenesis. Aberrations in several cytoskeletal proteins, such as neurofilaments, microtubules, and tau, have implicated in the pathogenesis of neurodegenerative diseases; could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Previous studies have suggested that tau protein and Aβ may serve as both diagnosis and prognosis biomarkers for the most common neurodegenerative disorder AD.
Glaucoma progression is with altered CSF levels of tau proteins. Several studies have also revealed links between AD and glaucoma; neuropathological progression occurs in the brain as well as in the eye and is mediated by a common neurodegenerative pathway. Tau is a cytosolic protein predominantly expressing in neurons and regulates microtubule stability within the axon.
Age and ocular hypertension glaucoma
It is increasingly that tau accumulates with age and ocular hypertension glaucoma; displays signature pathological features of tauopathies, leading to neurodegeneration. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG); primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels.
They observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonallopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients; elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, they conducted an experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC.
This result reinforces the potentiality of circulating DBN1 levels are increasing in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may a useful indicator for monitoring the progression of neurodegenerative diseases.