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GAN YIJING, ZAILONG CHI, JIA QU; Drebrin plasma levels elevated with RGCs axonopathy in glaucoma patients. Invest. Ophthalmol. Vis. Sci. 2019;60(9):681.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Developmentally-regulated brain protein (Drebrin, DBN1) is an evolutionarily conserved actin-binding protein that plays a prominent role in neurons. The purpose of this study is to discover the relationship between circulating DBN1 levels and axonal degeneration of RGCs in glaucoma patients.
The study was performed according to the tenets of the Declaration of Helsinki and in accordance with the ARVO Statement for the Use of Animals in Vision Research. A total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) were recruited and measured DBN1 plasma levels by enzyme-linked immunosorbent assay (ELISA). Retinal nerve fiber layer (RNFL) thickness was analyzed using optical coherence tomography (OCT). A total of 43 male Fischer rats aged 6-8 weeks (200-230g) were used to generate optic nerve crush (ONC) model. Western blot and immunofluorescent staining were used to detect the expression of DBN1 in the retina of ONC model. Two-tailed Student's t-test, one-way ANOVA and logistic regression were used for statistical analysis.
OCT analysis observed that RNFL defects (RNFLD) severe in POAG (72.30±2.36 µm, p<0.001) and moderate in PACG (96.19±2.73 µm, p<0.001) while close to normal in PS patients (99.97±2.51 µm, p=0.245). Elevated plasma DBN1 levels were observed in patients with primary glaucoma (p<0.001) but not in patients with PS (p=0.729) compared to nonaxonopathic controls. Circulating DBN1 levels correlated with RNFLD, especially in inferior temporal (IT, p=0.013) and superior temporal (ST, p=0.017) quadrants in glaucoma patients. In contrast, tau levels increased in all group of patients (p<0.001) but didn't correlate with RNFLD. DBN1 levels increased in serum (n=27, p=0.036) while reduced in the retina after ONC (n=16, p=0.045).
Our study reveals that circulating drebrin levels may reflect severity of RGCs injury in glaucoma patients. Combining the measurement of circulating DBN1 and tau levels may be a useful indicator for the diagnosis or evaluation of the severity of axonopathy in neurodegenerative diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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