Histochemical Analysis of Glaucoma Caused by a Myocilin Mutation in a Human Donor Eye.

Autor:	van der Heide CJ; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Alward WLM; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Flamme-Wiese M; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Riker M; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Syed NA; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Anderson MG; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; Center for Prevention and Treatment of Visual Loss, Iowa City Veterans Administration Medical Center, Iowa City, IA 52242, USA., Carter K; institute for Vision Research, University of Iowa, Iowa City, IA, USA., Kuehn MH; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Stone EM; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Mullins RF; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Fingert JH; institute for Vision Research, University of Iowa, Iowa City, IA, USA.; Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Jazyk:	angličtina
Zdroj:	Ophthalmology. Glaucoma [Ophthalmol Glaucoma] 2018 Sep-Oct; Vol. 1 (2), pp. 132-138. Date of Electronic Publication: 2018 Aug 17.
DOI:	10.1016/j.ogla.2018.08.004
Abstrakt:	Objective: Mutations in myocilin ( MYOC) may cause either juvenile open angle glaucoma (JOAG) or adult-onset primary open angle glaucoma (POAG). MYOC encodes a glycoprotein that is normally secreted from trabecular meshwork cells that regulate intraocular pressure. Prior in vitro, transgenic rodent, and organ culture experiments have suggested that abnormal accumulation of MYOC protein within trabecular meshwork cells is a key step in glaucoma pathophysiology. We investigated the pathogenesis of MYOC glaucoma by examining a donor eye from a patient with JOAG caused by a Tyr437His MYOC mutation. Design: Case-control, immunohistochemical study of a donor eye from a patient with JOAG caused by a Tyr437His MYOC mutation and age-matched control donor eyes. Subjects: An eye from a 59-year-old male with JOAG caused by a Tyr437His MYOC mutation and eyes from five donors (ages 51-66) with no known ocular disease were examined. Methods: Frozen fixed sections of the iridocorneal angle were prepared from the donor eyes of the MYOC glaucoma patient and control eyes. We used antibodies directed against MYOC, collagen IV, and BiP/GRP78 as well as wheat germ agglutinin and concanavalin A lectins to localize MYOC protein in the trabecular meshwork. Main Outcome Measure: Qualitative comparison of MYOC protein labeling and localization in the trabecular meshwork of donor eyes from a glaucoma patient with a MYOC mutation and from control subjects. Results: Using immunohistochemistry, we detected more abundant MYOC protein within the trabecular meshwork of the MYOC glaucoma patient's eye than in control eyes. We further localized MYOC protein within the trabecular meshwork cells of the MYOC glaucoma patient's eye by co-labeling with the endoplasmic reticulum (ER) marker GRP78 (BiP). Little to no MYOC was identified within the trabecular meshwork cells of control eyes. Minimal extracellular MYOC was detected in both MYOC glaucoma eyes and control eyes. Conclusions: This is the first histopathological analysis of an eye from a glaucoma patient with a MYOC mutation. Furthermore, this analysis supports our model of MYOC-associated glaucoma, in which MYOC mutations cause abnormal intracellular retention of MYOC within the ER of trabecular meshwork cells as a key step towards development of glaucoma.
Databáze:	MEDLINE
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