Journal article
MMP19 expression in the human optic nerve
Molecular vision, Vol.22, pp.1429-1436
2016
PMCID: PMC5166795
PMID: 28003733
Abstract
The defining feature of glaucoma is excavation of the optic nerve head; however, the mechanism of this loss of tissue is not well understood. We recently discovered a copy number variation upstream of ( ) in a large, autosomal dominant pedigree with a congenital malformation of the optic disc called cavitary optic disc anomaly (CODA). Patients with CODA have abnormal optic discs that exhibit an excavated shape similar to cupping seen in glaucoma. The goal of this study is to characterize the localization of MMP19 within the human optic nerve. The MMP19 protein in the optic nerve was evaluated with western blot analysis and with immunohistochemistry in sagittal and en face/cross sections of optic nerves obtained from healthy human donor eyes. The MMP19 protein was detected in the human optic nerve, retina, and RPE/choroid with western blot analysis, with highest expression in the retina and the optic nerve. Using immunohistochemistry, MMP19 was localized within the optic nerve to the extracellular space within the septa that separate bundles of optic nerve axons into fascicles. The presence of MMP19 within the optic nerve septa was further confirmed by the colocalization of MMP19 to this structure with type IV collagen. Strong labeling of MMP19 was also detected in the arachnoid layer of the optic nerve sheath. Finally, immunohistochemistry of the optic nerve cross sections demonstrated that MMP19 shows a peripheral to central gradient, with more abundant labeling along the edges of the optic nerve and in the arachnoid layer than in the center of the nerve. Abundant MMP19 was detected in the optic nerve head, the primary site of pathology in patients with CODA. The localization of MMP19 to the optic nerve septa is consistent with its predicted secretion and accumulation within the extracellular spaces of this tissue. Moreover, the lateral localization of MMP19 observed in the optic nerve cross sections suggests that it might have a role in regulating adhesion to the optic nerve to the scleral canal and remodeling the extracellular matrix that provides the structural integrity of the optic disc. Dysregulation of MMP19 production might, therefore, undermine the connections between the optic nerve and the scleral canal and cause a collapse of the optic disc and the development of CODA. Similar processes might also be at work in the formation of optic disc cupping in glaucoma.
Details
- Title: Subtitle
- MMP19 expression in the human optic nerve
- Creators
- Kathleen R Chirco - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IARalph J Hazlewood - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IA; Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, ILKathy Miller - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IAGrefachew Workalemahu - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IALee M Jampol - Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, ILG Robert Lesser - Department of Ophthalmology, William Beaumont School of Medicine, Oakland University, Royal Oak, MIRobert F Mullins - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IAMarkus H Kuehn - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IAJohn H Fingert - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Molecular vision, Vol.22, pp.1429-1436
- Publisher
- United States
- PMID
- 28003733
- PMCID
- PMC5166795
- ISSN
- 1090-0535
- eISSN
- 1090-0535
- Grant note
- R21 EY024621 / NEI NIH HHS
- Language
- English
- Date published
- 2016
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980033202771
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