Eye / Vision
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21683
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Browsing Eye / Vision by Author "Liu, Yang"
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Item C1q induction and glial activation following optic nerve injury(2017-03-14) Liu, Yang; Clark, Abbot; Allums, ElliottPurpose: Complement protein 1 subunit q (C1q) is a component of the C1 complex of the classical pathway of complement activation. It plays a role in synaptic development and pruning of central nervous system, as well as in the pathogenesis of various neurodegenerative diseases. In this study, we characterized C1q expression in C57BL/6J mice in an optic nerve crush (ONC) model of neurodegeneration. We also examined glial activation to determine possible sources of the increased C1q expression. Methods: Acute injury was induced in adult C57BL/6J mice by intraorbital ONC performed approximately 1 mm posterior to the optic nerve head with self-closing forceps for four seconds. C1q expression and glial activation (GFAP) was determined at 3 and 7 days post ONC by immunohistochemistry (IHC) as well as Western Blotting. Results: C1q expression increased in the crush site in the optic nerve, the inner plexiform layer (IPL) and the outer plexiform layer (OPL) of the retina 3 days after ONC. C1q expression further increased 7 days after ONC in the crush site, IPL, OPL, as well as the ganglion cell layer (GCL). Optic nerve injury increased glial fibrillary acidic protein (GFAP) expression in the GCL layer, extending through the retinal layers, 7 days post ONC and ED1 expression in the crush site 3 and 7 days following ONC. Conclusions: This study shows that C1q may play a role in neurodegeneration and could have potential as a therapeutic target. Glial cells may be responsible for the increased expression in C1q following ONC.Item Glucocorticoid receptor GRβ regulates glucocorticoid-induced ocular hypertension and glaucoma in mice(2017-03-14) Liu, Yang; Millar, J. Cameron; Clark, Abbot; Patel, GaurangPurpose: Glucocorticoid (GC) induced ocular hypertension (OHT) is a serious side effect of prolonged GC therapy and if left untreated it can lead to iatrogenic glaucoma and permanent vision loss. The Alternatively spliced isoform of glucocorticoid receptor GRβ acts as a dominant negative regulator of GC activity. Our previous studies have shown that GRβ regulates GC responsiveness and that overexpressing GRβ in trabecular meshwork (TM) cells inhibits GC-induced and glaucomatous damage in TM cells. The purpose of this study was to determine whether increased expression of GRβ can reverse GC-induced OHT in mice. Methods: Mouse trabecular meshwork cells (MTM) were transduced with Ad5.null or Ad5.hGRβ expression vectors at MOI-50. After 24 hours MTM cells were treated with dexamethasone (DEX) or vehicle control (0.1% ethanol). To generate GC-OHT, C57BL/6J mice received weekly bilateral periocular (administrated through conjunctival fornix) injections of dexamethasone acetate (DEX-Ac, 200ug/eye). Several weeks after DEX-Ac administration, mouse eyes were injected intravitreally with Ad5.null or Ad5.hGRβ expression vectors (3x107 pfu/eye) to transduce the TM. Nighttime intraocular pressure (IOP) was measured using a TonoLab rebound tonometer, and outflow facilities were measured in living mice using our constant flow infusion technique. Fibronectin and collagen I expression were evaluated using immunoblotting of mouse anterior segment tissues. The unpaired Student’s t-test (2-tailed) and One-way ANOVA were used for statistical analysis. Results: DEX treatment of MTM cells increased fibronection expression, whereas transduction of MTM cells with Ad5.hGRβ maintained fibronectin expression at control levels as shown by immunocytochemistry. DEX-Ac significantly increased IOP from days 3-44 (n=23, p Conclusion: Overexpression of GRβ in the TM of mouse eyes reversed GC-OHT. GRβ gene therapy may be a useful therapeutic approach to treat GC-OHT and glaucoma.