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Norimitsu Ban, Ying-Bo Shui, Carla J Siegfried, Abdoulaye Sene, Jonathan B Lin, Andrea Santeford, Jun Yoshino, Rajendra S Apte; Growth differentiation factor 15 (GDF15) in aqueous humor is a novel biomarker for glaucoma progression.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6020.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is a leading cause of progressive vision loss and blindness worldwide. Despite extensive research, a specific and sensitive biomarker of glaucoma progression has remained elusive. We hypothesized that a protein secreted by the retina into the aqueous humor (AH) may be a useful biomarker for retinal ganglion cell (RGC) death and glaucoma progression.
Using a cytokine focused expression qPCR array, we compared the mouse optic nerve crush (ONC) model to the light exposure induced retinal degeneration (RD) model and the endotoxin induced uveitis (EIU) model in order to identify factors that were unique to RGC death. Based on the array results, we measured growth differentiation factor 15 (GDF15) concentration in AH of mice using the ONC model by ELISA. Results were validated in glaucoma patients (n = 27) and controls without glaucoma (n = 18).
Although there were some cytokines that were altered in either 2 or all 3 models, GDF15 was the only cytokine upregulated uniquely in the ONC model. GDF15 concentration in AH of mouse ONC eye was 2-fold higher than the unaffected contralateral eye (39.5 ± 3.9 (SD) vs 20.8 ± 1.8 (SD) pg/ml; p<0.01). GDF15 concentration in AH of glaucoma patients was significantly higher than control patients (185.2 ± 43.8 (SEM) vs 10.19 ± 7.1 (SEM) pg/ml; p<0.01).
Our array results suggest that GDF15 secreted by retina may be a specific biomarker of RGC cell death. We have also demonstrated that GDF15 is significantly increased in AH of mouse ONC model as well as glaucoma patients. Therefore GDF15 in aqueous humor correlates with RGC death and can be a useful and accessible biomarker for glaucoma progression.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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