Table 1A.
Selected Trabecular Meshwork Relevant Genes Altered by Wild-Type and Mutant Myocilin
| Gene name | Symbol | FC | RNA/protein origin | Overexpress model | Species | Analysis | Function | Citation |
|---|---|---|---|---|---|---|---|---|
| Wild-type Myocilin | ||||||||
| Podoplanin | PDPN | 4.7 | HTM cells* | Adh.myocWT | Human | AffyU133P2.0 | Lymph.marker/ Rho activ. | Kennedy 2012 |
| Prostaglandin D2 synthase | PTGDS | 3.4 | HTM cells* | Adh.myocWT | Human | AffyU133P2.0 | Neuromodulator | Kennedy 2012 |
| Chitinase 3-like 1 | CHI3L1 | 3.0 | HTM cells* | Adh.myocWT | Human | AffyU133P2.0 | Cartilage ECM | Kennedy 2012 |
| αB-Crystallin | CRYAB | 1.8 | HTM cells* | Adh.myocWT | Human | AffyU133P2.0 | Chaperone | Kennedy 2012 |
| Matrix metallopeptidase 1 | MMP1 | 26.0 | HTM cells** | AdhTIG3.WT | Human | AffyU133 A | ECM remodeling | Borrás 2006 |
| Thrombomodulin | THBD | 20.0 | HTM cells** | AdhTIG3.WT | Human | AffyU133 A | Binds thrombin/clotting | Borrás 2006 |
| Angiopoietin 2 | ANGPT2 | 39.0 | HTM cells** | AdhTIG3.WT | Human | AffyU133 A | Pro-angiogenic | Borrás 2006 |
| Swiss cheese | sws | 34.0 | Transgenic* | UAS-WT | Drosophila | AffyDros 2.0 | Neurodegenerative prt. | Borrás 2003 |
| Aqp1049 | CG4019 | −1.8 | Transgenic* | UAS-WT | Drosophila | AffyDros 2.0 | Water chanel activity | Borrás 2003 |
| Cytochrome P450 | CYP315A1 | −2.6 | Transgenic* | UAS-WT | Drosophila | AffyDros 2.0 | Detoxification | Borrás 2003 |
| Conexin46 | Gja3 | 5.0 | Transgenic** | βB1-Cry-Myoc | Mouse | Affy 430.2.0A | Gap junct/cell-cell sign. | Paper 2008 |
| αB-Crystallin | Cryab | 1.9 | Transgenic** | βB1-Cry-Myoc | Mouse | Affy 430.2.0A | Response to heat | Paper 2008 |
| Spondin | Spon2 | 1.6 | Transgenic** | βB1-Cry-Myoc | Mouse | Affy 430.2.0A | Cell adhesion | Paper 2008 |
| Homeobox protein Six1 | Six1 | −1.8 | Transgenic** | βB1-Cry-Myoc | Mouse | Affy 430.2.0A | Transcription factor | Paper 2008 |
| Neural Wiskott-Aldrich prt. | Wasl | −1.8 | Transgenic** | βB1-Cry-Myoc | Mouse | Affy 430.2.0A | Cytoskeleton signaling | Paper 2008 |
| Carcinoembryonic antigen1 | Ceacam1 | −1.7 | Transgenic** | βB1-Cry-Myoc | Mouse | Affy 430.2.0A | Cell adhesion | Paper 2008 |
| Myocilin mutants | ||||||||
| Q368X | ||||||||
| Prot disulfide isomerase A4 | PDIA4 | 2.1 | HTM cells* | Adh.Q368X | Human | AffyU133P2.0 | Chaperone | Kennedy 2012 |
| Secret frizz-related prot 1 | SFRP1 | −2.5 | HTM cells* | Adh.Q368X | Human | AffyU133P2.0 | Wnt signaling | Kennedy 2012 |
| Matrix Gla protein | MGP | −2.0 | HTM cells* | Adh.Q368X | Human | AffyU133P2.0 | Inhibitor of calcification | Kennedy 2012 |
| Lysyl oxidase-like 1 | LOXL1 | −2.0 | HTM cells* | Adh.Q368X | Human | AffyU133P2.0 | Elastin network | Kennedy 2012 |
| Heat shock prot 90B1 (GRP94) | HSP90B1 | 3.3 | HTM cells* | Adh.Q368X | Human | AffyU133P2.0 | Unfo Prot Respon (UPR) | Kennedy 2012 |
| Calreticulin | CALR | 2.3 | HTM cells* | Adh.Q368X | Human | AffyU133P2.0 | Unfo Prot Respon (UPR) | Kennedy 2012 |
| Glycoprotein 93 | Gp93 | up | Transgenic* | UAS-Q368X | Drosophila | AffyDros 2.0 | Unfo Prot Respon (UPR) | Carbone 2009 |
| Calreticulin | Crc | up | Transgenic* | UAS-Q368X | Drosophila | AffyDros 2.0 | Unfo Prot Respon (UPR) | Carbone 2009 |
| R342K | ||||||||
| Ras-related protein 39B | RAB39B | 3.2 | HTM cells* | Adh.R342K | Human | AffyU133P2.0 | Vesicular trafficking | Kennedy 2012 |
| D380N | ||||||||
| Matrix metallopeptidase 1 | MMP1 | −5.5 | HTM cells* | Adh.D380N | Human | AffyU133P2.0 | ECM remodeling | Kennedy 2012 |
| Fibronectin 1 | FN1 | 1.8 | HTM cells* | Adh.D380N | Human | AffyU133P2.0 | Cell adhesion | Kennedy 2012 |
| Synuclein alpha | SNCA | 2.5 | HTM cells* | Adh.D380N | Human | AffyU133P2.0 | Presynaptic signal | Kennedy 2012 |
| K423E | ||||||||
| Insulin-like growth factor 1 | IGF1 | 3.9 | HTM cells* | Adh.K423E | Human | AffyU133P2.0 | Signaling hormone | Kennedy 2012 |
| Cytochrome P450, 1B1 | CYP1B1 | −2.7 | HTM cells* | Adh.K423E | Human | AffyU133P2.0 | Detoxification | Kennedy 2012 |
| Q368X, R342K,D380N,K423E (of 73 shared) | ||||||||
| Chemokine (C-X-C motif)12 | CXCL12 | −3.0 | HTM cells* | Adh.Q368X | Human | AffyU133P2.0 | Signaling cytokine | Kennedy 2012 |
| Cystatin A (Stefin A) | CSTA | 3.4 | HTM cells* | Adh.R342K | Human | AffyU133P2.0 | Protein processing | Kennedy 2012 |
| Endothelin 1 | EDN1 | −1.6 | HTM cells* | Adh.D380N | Human | AffyU133P2.0 | Vasoactive peptides | Kennedy 2012 |
| Stanniocalcin 1 | STC1 | −1.8 | HTM cells* | Adh.K423E | Human | AffyU133P2.0 | Calcium homeostasis | Kennedy 2012 |
| P370L | ||||||||
| Glucose-reg Prot78 (BIP) | GRP78 | −1.5 | HTM cells* | pcDNA3.P370L | Human | WB | Unfo Prot Respon (UPR) | Wang 2007 |
| Y437H | ||||||||
| Glucose-reg Prot78 (BIP) | GRP78 | up | HEK 293*. | Y437H | Human | WB | Unfo Prot Respon (UPR) | Joe 2010 |
| Protein disulfide isomerase | PDI | up | HEK 293* | Y437H | Human | WB | Chaperone | Joe 2010 |
| I477N | ||||||||
| Glucose-reg Prot94 (HSP90B1) | GRP94 | up | HEK 293**. | I477N | Human | co-IP | Unfo Prot Respon (UPR) | Suntharalingam 2012 |
| Protein disulfide isomerase | PDI | up | HEK 293** | I477N | Human | WB | Chaperone | Joe 2010 |
| Glucose-reg Prot78 (BIP) | GRP78 | up | HEK 293** | I477N | Human | WB | Unfo Prot Respon (UPR) | Joe 2010 |
ECM 
Protein synthesis/modification 
Stress / defense 
Cytoskeleton/structural 
Signaling/cytokines 
Calcification
HTM cells*, primary human trabecular meshwork cells derived directly from TM explants; HTM cells**, primary human trabecular meshwork cells derived from collagenase treatment of TMs.
Transgenic*, Heads from transgenic flies.
Transgenic**, Mouse eyes (minus lens) from transgenic mice.
HEK 293*, HEK 293 Tet-On stably transfected with pTRE-Y437H MYOC.
HEK 293**, HEK 293 Tet-On stably transformed with pTRE-I477N MYOC.
HTMs, human trabecular meshworks; WB, Western blot; ECM, extracellular matrix.