Autoantibodies may serve as glaucoma biomarkers
The loss of autoantibodies may serve as useful biomarkers for glaucoma, according to Nadine von Thun Und Hohenstein-Blaul, Johannes Gutenberg University Mainz, Mainz, Germany, and colleagues.
“We conclude that the absence of some autoantibodies in glaucoma patients reflects a loss of the protective potential of natural autoimmunity and may thus encourage neurodegenerative processes,” they wrote in the journal Eye.
The researchers showed a correlation between changes in autoantibody profiles and the loss of retinal ganglion cells independent of IOP.
While an elevated IOP is the most common known risk factor for glaucoma, most people with an elevated IOP do not develop the disease.
For this reason, researchers have reasoned that other risk factors play a more important role in the development of the condition, especially in those with normal IOP.
Risk factors may include age, sex, ethnicity, oxidative stress, systemic and ocular vascular factors, elevated glutamate concentration or nitric oxide levels, and autoimmune conditions. However, IOP remains the only risk factor susceptible to modification as a treatment for glaucoma.
To date, most potential screening tests for glaucoma have an estimated 85% specificity and most patients suffer from glaucoma for more than 10 years before diagnosis, partly as a result of ineffective screening. During that time, as many as half their retinal ganglion cells may be lost.
Studies suggest up to half of glaucoma cases remain undiagnosed in developed countries, and 9 out of 10 worldwide, they wrote. Earlier diagnosis might prevent many cases of blindness. Researchers are looking for biomarkers that can be used to catch glaucoma cases earlier.
Von Thun Und Hohenstein-Blaul and her colleagues undertook an examination of proteomic changes in the retinas of glaucoma patients using mass spectrometry.
They found distinct changes in 10% of proteins supporting the involvement of three functional classes of in glaucoma: mitochondrial, stress and nucleus proteins, suggesting an impairment of energy metabolism, stress response, and gene expression alterations.
The researchers have also found evidence of autoimmune involvement in the pathogenesis of glaucoma. They have detected disease-specific changes in complex expression levels of immunoglobulin C (IgC) autoantibodies against ocular tissue in the sera and aqueous humour of patients with primary open-angle glaucoma, normal tension glaucoma, and ocular hypertension.
These profiles are stable and can be found in populations from different countries, they added.
Not only are the levels of some antibodies elevated, but others are lowered, the researchers found. For example, they found up-regulation of autoantibodies against alpha-fodrin, HSP70 and myelin basic protein, and down-regulation of antibodies against αB-Cyrstallin and Vimentin.