We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma.

Mutations in myocilin (MYOC) are the most common genetic cause of primary open angle glaucoma (POAG), but the mechanisms underlying MYOC-associated glaucoma are not fully understood. Here, we report the development of a transgenic mouse model of POAG caused by the Y437H MYOC mutation; the mice are referred to herein as Tg-MYOC(Y437H) mice. Analysis of adult Tg-MYOC(Y437H) mice, which we showed express human MYOC containing the Y437H mutation within relevant eye tissues, revealed that they display glaucoma phenotypes (i.e., elevated intraocular pressure [IOP], retinal ganglion cell death, and axonal degeneration) closely resembling those seen in patients with POAG caused by the Y437H MYOC mutation. Mutant myocilin was not secreted into the aqueous humor but accumulated in the ER of the trabecular meshwork (TM), thereby inducing ER stress in the TM of Tg-MYOC(Y437H) mice. Furthermore, chronic and persistent ER stress was found to be associated with TM cell death and elevation of IOP in Tg-MYOC(Y437H) mice. Reduction of ER stress with a chemical chaperone, phenylbutyric acid (PBA), prevented glaucoma phenotypes in Tg-MYOC(Y437H) mice by promoting the secretion of mutant myocilin in the aqueous humor and by decreasing intracellular accumulation of myocilin in the ER, thus preventing TM cell death. These results demonstrate that ER stress is linked to the pathogenesis of POAG and may be a target for treatment in human patients.

Pubmed ID: 21821918 RIS Download

Mesh terms: Animals | Apoptosis | Cells, Cultured | Cytoskeletal Proteins | Endoplasmic Reticulum | Eye Proteins | Glaucoma, Open-Angle | Glycoproteins | Humans | Intraocular Pressure | Mice | Mice, Transgenic | Mutation | Phenotype | Phenylbutyrates | Stress, Physiological | Trabecular Meshwork | Transgenes | Unfolded Protein Response

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NEI NIH HHS, Id: R01 EY019485
  • Agency: NEI NIH HHS, Id: R01 EY10564
  • Agency: NEI NIH HHS, Id: R01 EY018825
  • Agency: NEI NIH HHS, Id: R01 EY010564
  • Agency: NEI NIH HHS, Id: R01 EY017673
  • Agency: Howard Hughes Medical Institute, Id: R01 EY022044
  • Agency: NEI NIH HHS, Id:

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.