Methods for analyzing endoplasmic reticulum stress in the trabecular meshwork of glaucoma models

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

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

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.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages121-134
Number of pages14
DOIs
StatePublished - 1 Jan 2018

Publication series

NameMethods in Molecular Biology
Volume1695
ISSN (Print)1064-3745

Keywords

  • Chemical induction of ER stress in TM
  • ER stress in glaucomatous TM
  • Genetic manipulation of ER stress
  • Glucocorticoid-induced ocular hypertension
  • Myocilin induced ER stress
  • Unfolded protein response (UPR) target genes
  • XBP-1 splicing

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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 Methods in Molecular Biology (pp. 121-134). (Methods in Molecular Biology; Vol. 1695). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-7407-8_12