Abstract
Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Aberrations in several cytoskeletal proteins, such as tau have been implicated in the pathogenesis of neurodegenerative diseases, could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Developmentally regulated brain protein (Drebrin or DBN1) is an evolutionarily conserved actin-binding protein playing a prominent role in neurons and is implicated in neurodegenerative diseases. However, the relationship between circulating DBN1 levels and RGC degeneration in glaucoma patients remains unclear. In our preliminary study, we detected drebrin protein in the plasma of glaucoma patients using proteomic analysis. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels. We observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonaxonopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients, elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, we conducted experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC. This result reinforces the potentiality of circulating DBN1 levels are increased in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may be a useful indicator for monitoring progression of neurodegenerative diseases.
Highlights
Glaucoma comprises a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells (RGCs) (Weinreb et al, 2014), resulting in characteristic changes in the optic nerve head (ONH) and retinal nerve fiber layer (RNFL), and associated visual field (VF) defects (Venkataraman et al, 2010; Almasieh et al, 2012; Chen et al, 2017; Choi et al, 2017)
We demonstrated that developmentally regulated brain protein (DBN1) plasma levels increased significantly in glaucoma patients with neurodegeneration and were correlated with RNFLD
Glaucoma represents a group of neurodegenerative diseases characterized by RGC degeneration (Almasieh et al, 2012; Weinreb et al, 2014; Choi et al, 2017)
Summary
Glaucoma comprises a group of optic neuropathies characterized by progressive degeneration of RGCs (Weinreb et al, 2014), resulting in characteristic changes in the ONH and RNFL, and associated VF defects (Venkataraman et al, 2010; Almasieh et al, 2012; Chen et al, 2017; Choi et al, 2017). The biological basis of glaucoma is poorly understood, and the factors contributing to its progression have not been fully characterized (Nickells et al, 2012). Diagnosis of glaucoma is made by a combination of identifying characteristic changes of the RGCs and ONH, functional testing such as VFs, and structural imaging of the retina (Mantravadi and Vadhar, 2015). Diagnosis and treatment of glaucoma are key to preventing vision loss. No biochemistry indexes have been used for diagnosis or evaluation of the severity of axonal injury or axonopathy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
