Publications -- Gulab Zode
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/31718
This collection is limited to articles published under the terms of a creative commons license or other open access publishing agreement since 2016. It is not intended as a complete list of the author's works.
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Browsing Publications -- Gulab Zode by Author "Clark, Abbot F."
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Item CNS axonal degeneration and transport deficits at the optic nerve head precede structural and functional loss of retinal ganglion cells in a mouse model of glaucoma(BioMed Central Ltd., 2020-08-27) Maddineni, Prabhavathi; Kasetti, Ramesh B.; Patel, Pinkal D.; Millar, J. Cameron; Kiehlbauch, Charles; Clark, Abbot F.; Zode, Gulab S.BACKGROUND: Glaucoma is a leading neurodegenerative disease affecting over 70 million individuals worldwide. Early pathological events of axonal degeneration and retinopathy in response to elevated intraocular pressure (IOP) are limited and not well-defined due to the lack of appropriate animal models that faithfully replicate all the phenotypes of primary open angle glaucoma (POAG), the most common form of glaucoma. Glucocorticoid (GC)-induced ocular hypertension (OHT) and its associated iatrogenic open-angle glaucoma share many features with POAG. Here, we characterized a novel mouse model of GC-induced OHT for glaucomatous neurodegeneration and further explored early pathological events of axonal degeneration in response to elevated IOP. METHODS: C57BL/6 J mice were periocularly injected with either vehicle or the potent GC, dexamethasone 21-acetate (Dex) once a week for 10 weeks. Glaucoma phenotypes including IOP, outflow facility, structural and functional loss of retinal ganglion cells (RGCs), optic nerve (ON) degeneration, gliosis, and anterograde axonal transport deficits were examined at various stages of OHT. RESULTS: Prolonged treatment with Dex leads to glaucoma in mice similar to POAG patients including IOP elevation due to reduced outflow facility and dysfunction of trabecular meshwork, progressive ON degeneration and structural and functional loss of RGCs. Lowering of IOP rescued Dex-induced ON degeneration and RGC loss, suggesting that glaucomatous neurodegeneration is IOP dependent. Also, Dex-induced neurodegeneration was associated with activation of astrocytes, axonal transport deficits, ON demyelination, mitochondrial accumulation and immune cell infiltration in the optic nerve head (ONH) region. Our studies further show that ON degeneration precedes structural and functional loss of RGCs in Dex-treated mice. Axonal damage and transport deficits initiate at the ONH and progress toward the distal end of ON and target regions in the brain (i.e. superior colliculus). Most of anterograde transport was preserved during initial stages of axonal degeneration (30% loss) and complete transport deficits were only observed at the ONH during later stages of severe axonal degeneration (50% loss). CONCLUSIONS: These findings indicate that ON degeneration and transport deficits at the ONH precede RGC structural and functional loss and provide a new potential therapeutic window for rescuing neuronal loss and restoring health of damaged axons in glaucoma.Item Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms(ARVO Journals, 2022-02) McDowell, Colleen M.; Kizhatil, Krishnakumar; Elliott, Michael H.; Overby, Darryl R.; van Batenburg-Sherwood, Joseph; Millar, J. Cameron; Kuehn, Markus H.; Zode, Gulab S.; Acott, Ted S.; Anderson, Michael G.; Bhattacharya, Sanjoy K.; Bertrand, Jacques A.; Borras, Terete; Bovenkamp, Diane E.; Cheng, Lin; Danias, John; De Ieso, Michael Lucio; Du, Yiqin; Faralli, Jennifer A.; Fuchshofer, Rudolph; Ganapathy, Preethi S.; Gong, Haiyan; Herberg, Samuel; Hernandez, Humberto; Humphries, Peter; John, Simon W. M.; Kaufman, Paul L.; Keller, Kate E.; Kelley, Mary J.; Kelly, Ruth A.; Krizaj, David; Kumar, Ajay; Leonard, Brian C.; Lieberman, Raquel L.; Liton, Paloma; Liu, Yutao; Liu, Katy C.; Lopez, Navita N.; Mao, Weiming; Mavlyutov, Timur A.; McDonnell, Fiona; McLellan, Gillian J.; Mzyk, Philip; Nartey, Andrews; Pasquale, Louis R.; Patel, Gaurang C.; Pattabiraman, Padmanabhan P.; Peters, Donna M.; Raghunathan, Vijaykrishna; Rao, Ponugoti Vasantha; Rayana, Naga; Raychaudhuri, Urmimala; Reina-Torres, Ester; Ren, Ruiyi; Rhee, Douglas; Chowdhury, Uttio Roy; Samples, John R.; Samples, E. Griffen; Sharif, Najam; Schuman, Joel S.; Sheffield, Val C.; Stevenson, Cooper H.; Soundararajan, Avinash; Subramanian, Preeti; Sugali, Chenna Kesavulu; Sun, Yang; Toris, Carol B.; Torrejon, Karen Y.; Vahabikashi, Amir; Vranka, Janice A.; Wang, Ting; Willoughby, Colin E.; Xin, Chen; Yun, Hongmin; Zhang, Hao F.; Fautsch, Michael P.; Tamm, Ernst R.; Clark, Abbot F.; Ethier, C. Ross; Stamer, W. DanielDue to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.Item Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork(Springer Nature, 2017-11-02) Kasetti, Ramesh B.; Maddineni, Prabhavathi; Millar, J. Cameron; Clark, Abbot F.; Zode, Gulab S.Increased synthesis and deposition of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) is associated with TM dysfunction and intraocular pressure (IOP) elevation in glaucoma. However, it is not understood how ECM accumulation leads to TM dysfunction and IOP elevation. Using a mouse model of glucocorticoid (GC)-induced glaucoma, primary human TM cells and human post-mortem TM tissues, we show that increased ECM accumulation leads to endoplasmic reticulum (ER) stress in the TM. The potent GC, dexamethasone (Dex) increased the secretory protein load of ECM proteins in the ER of TM cells, inducing ER stress. Reduction of fibronectin, a major regulator of ECM structure, prevented ER stress in Dex-treated TM cells. Overexpression of fibronectin via treatment with cellular fibronectin also induced chronic ER stress in primary human TM cells. Primary human TM cells grown on ECM derived from Dex-treated TM cells induced ER stress markers. TM cells were more prone to ER stress from ECM accumulation compared to other ocular cell types. Moreover, increased co-localization of ECM proteins with ER stress markers was observed in human post-mortem glaucomatous TM tissues. These data indicate that ER stress is associated with increased ECM accumulation in mouse and human glaucomatous TM tissues.