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Regulation of TIGR/MYOC gene expression in human trabecular meshwork cells
J R Polansky1, D J Fauss, C C Zimmerman
1Department of Ophthalmology, University of California Medical Center, San Francisco 94143-0730, USA. drcarin@itsa.ucsf.edu
Eye (London, England)
|October 12, 2000
Summary
Glucocorticoid-induced TIGR gene expression in eye cells, linked to glaucoma, is reduced by protective factors like bFGF and T3. Mutations in the TIGR gene
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Genetics
Background:
- Glucocorticoid (GC) treatment of human trabecular meshwork (HTM) cells induces proteins and glycoproteins, mimicking corticosteroid eyedrop effects on intraocular pressure.
- The Trabecular Meshwork Inducible Glucocorticoid Response (TIGR) gene's role in glaucoma pathogenesis is suggested by its induction in HTM cells.
Purpose of the Study:
- To investigate the regulation of TIGR gene expression by endogenous factors and the impact of TIGR mutations on cellular function.
- To explore potential mechanisms linking environmental and genetic factors in glaucoma.
Main Methods:
- HTM cells were treated with glucocorticoids, bFGF, and T3 to assess TIGR expression.
- TIGR gene mutations, including those in the olfactomedin (OLF) homology domain, were analyzed.
- TIGR-green fluorescent protein (GFP) fusions were used in transfection studies to examine protein distribution and processing.
Main Results:
- Basic fibroblast growth factor (bFGF) and triiodothyronine (T3) significantly reduced GC-induced TIGR expression in HTM cells.
- Mutations within the TIGR gene's OLF domain altered protein intermediate patterns and distribution.
- Deletion or mutation of the OLF domain in TIGR-GFP fusions led to altered protein distribution and potentially activated stress/apoptotic pathways.
Conclusions:
- Endogenous factors like bFGF and T3 may counteract GC-induced TIGR expression, potentially offering a protective effect in glaucoma.
- TIGR gene mutations, particularly in the OLF domain, can disrupt protein biogenesis and cellular homeostasis, contributing to glaucoma pathogenesis.
- Stress and apoptotic pathways may be activated in HTM cells due to TIGR gene alterations, highlighting a mechanism for environmental and genetic interactions in glaucoma.