Abstract
Purpose :
Although glaucoma is a leading cause of irreversible blindness worldwide, the pathophysiology underlying neurodegeneration in primary open-angle glaucoma (POAG) remains poorly understood. We hypothesize that loss of retinal ganglion cells (RGCs) in POAG may be attributed to subclinical neuroinflammation. To test this, we analyzed serum levels of autoantibodies that recognize neural specific proteins in patients with high-pressure POAG and normal-tension subtype of POAG (NTG).
Methods :
With approval by the Institutional Review Board, age-matched patients with POAG (n=9), NTG (n=4) and healthy controls (n=13) were recruited from the Duke Eye Center. Demographic and clinical data were retrieved from electronic medical records. Exclusion criteria included history of neurodegenerative diseases (e.g. Alzheimer’s, Parkinson’s diseases), non-glaucomatous optic neuropathies, retinopathies, or neuronal loss due to brain diseases (e.g. tumors, strokes). Western blotting and ELISA were utilized to quantify autoantibodies that specifically recognize neuronal proteins (e.g. tau, MAP, etc). Non-neuronal proteins such as GFAP were included for comparison. Triplicate optical density measurements were averaged, normalized to total IgG levels, and compared using 2-sided t-tests and Pearson correlation using SigmaStat software for statistical significance (p<0.05).
Results :
Mean age of subjects were 68.8 years, and 46.2% of these patients were females. Average time after initial glaucoma diagnosis was 9.9 years in the POAG group and 10.3 years in the NTG group. Mean maximal intraocular pressures were 31.8 (POAG), 18.0 (NTG) and 16.4 mmHg (Control). Average number of glaucoma drops used was 2.6 (POAG) and 2.3 (NTG). Many autoantibodies levels were found to be significantly higher in glaucoma patients. These were in the order of GFAP>MAP>NFP>CaMkII>MAG>MBP for POAG while NTG was in the order of tau>MAP>MAG>GFAP>NFP.
Conclusions :
This study provides preliminary evidence supporting subclinical neuroinflammation as a possible neurodegenerative mechanism in POAG. Interestingly, autoantibody profiles for POAG and NTG were different. Our work may facilitate the development of serum biomarkers as diagnostic and therapeutic targets.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.