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Methods for Analyzing Endoplasmic Reticulum Stress in the Trabecular Meshwork of Glaucoma Models

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Glaucoma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1695))

Abstract

The pathological mechanisms underlying increased outflow resistance at the trabecular meshwork (TM) that is responsible for elevating intraocular pressure (IOP) have not been fully delineated. Recent studies have shown that progressive accumulation of misfolded proteins and induction of endoplasmic reticulum (ER) stress is associated with the pathophysiology of glaucomatous TM damage and IOP elevation. We have shown that known causes of human glaucoma, including expression of mutant myocilin or dexamethasone treatment induce abnormal protein accumulation and ER stress in the TM in vitro and in vivo models. To cope up with abnormal protein accumulation, TM cells activate a cytoprotective pathway of unfolded protein response (UPR). However, chronic ER stress can lead to TM dysfunction and IOP elevation. Using cell culture, mouse models, and human postmortem tissues as well as genetic and pharmacological manipulations, we have analyzed ER stress and UPR mediators in the glaucomatous TM damage and IOP elevation. In this chapter, we have described a detailed protocol for the analysis of protein misfolding and ER stress in TM cells and tissues and its association with glaucomatous TM damage and IOP elevation.

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Acknowledgments

This work was supported by funding from the following grants and organizations: National Eye Institute, EY022077 (R00) and EY026177 (R01) to G. S. Zode and funding from the North Texas Eye Research Institute.

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Authors and Affiliations

  1. The North Texas Eye Research Institute, CBH-413, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA

    Prabhavathi Maddineni, Ramesh B. Kasetti & Gulab S. Zode

Authors
  1. Prabhavathi Maddineni
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  2. Ramesh B. Kasetti
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  3. Gulab S. Zode
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Corresponding author

Correspondence to Gulab S. Zode .

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Editors and Affiliations

  1. Department of Ophthalmology, Massachusetts Eye and Ear Infirmary/Schepens Eye, Research Institute, Harvard Medical School, Boston, Massachusetts, USA

    Tatjana C. Jakobs

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Maddineni, P., Kasetti, R.B., Zode, G.S. (2018). Methods for Analyzing Endoplasmic Reticulum Stress in the Trabecular Meshwork of Glaucoma Models. In: Jakobs, T. (eds) Glaucoma. Methods in Molecular Biology, vol 1695. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7407-8_12

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  • DOI: https://doi.org/10.1007/978-1-4939-7407-8_12

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7406-1

  • Online ISBN: 978-1-4939-7407-8

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