Autoantibodies may serve as glaucoma biomarkers
To explore the influence of these autoimmune responses, the researchers immunised animals with antibodies against some of the proteins in question, such as HSP60, HSP27, and MBP, resulting in glaucomatous damage with distinct retinal ganglion cell loss.
In another experiment, they attached a silicone loop around the limbi of animal eyes to temporarily increase the IOP. Pressure returned to normal after this manipulation, demonstrating that this does not create angle-closure glaucoma.
They also found that these intermittent IOP elevations caused degeneration in the optic nerve and the retina and changed IgC autoantibody activity. Attempts to modulate the immune response with the B lymphocyte inhibitor Belimumab did not increase axonal and retinal ganglion cell survival.
However, these authors have done in vitro studies showing that antibodies down-regulated in glaucoma patients, for example, antibodies against glial fibrillary acidic protein, 14-3-3 or gamma (γ)-synuclein, have protective effects on immortalized neuroretinal cells and increase their viability under stress conditions.
By incubating retinal organ culture from adolescent pigs with antibodies for 24 h they found a protective effect on retinal ganglion cells for anti-GFAP and anti- γ-synuclein. They did not find this effect for anti-myoglobin, which they used as a control.
They also found increased levels of glutamine synthetase in the antibody-treated retinal explants, a marker of Müller cells. Müller cells are essential for retinal ganglion cell survival and play a part in recycling neurotransmitters, homeostasis of the extracellular environment, removal of metabolic end products, and the supply of neurotrophic and antioxidant factors.
It is not clear whether such these changes in autoantibodies cause glaucoma or simply result from it, but they do seem promising as biomarkers for the disease, the researchers wrote.
Using a targeted antigen microarray, they differentiated sera of people with primary open angle glaucoma from people without glaucoma based on antibody profiles, with a sensitivity and specificity better than 93%.
“This represents an enormous diagnostic precision when compared to established screening tests,” they wrote. “Furthermore, the correlation between damage and changes in the autoantibody reactivity found in the intermittent ocular hypertension model suggests that autoantibody profiling could also be used as biomarkers for progression and severity of the disease.”