July 1999
Volume 40, Issue 8
Letters to the Editor  |   July 1999
TIGR and Stretch in the Trabecular Meshwork
Author Affiliations
  • Adam Booth
    University of California, San Francisco
  • Thai Nguyen
    University of California, San Francisco
  • Jon Polansky
    University of California, San Francisco
Investigative Ophthalmology & Visual Science July 1999, Vol.40, 1888-1889. doi:
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      Adam Booth, Thai Nguyen, Jon Polansky; TIGR and Stretch in the Trabecular Meshwork. Invest. Ophthalmol. Vis. Sci. 1999;40(8):1888-1889.

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      © ARVO (1962-2015); The Authors (2016-present)

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Tumminia and colleagues 1 recently suggested that human trabecular meshwork cells, used to model juxtacanalicular cells, respond to mechanical stretch by an alteration in their cytoskeletal network and signaling cascades. They further postulated that, in the long-term, the pressure-induced signals could cause“ altered secretion or degradation through changes in the composition of the extracellular matrix in the extracellular flow pathway that may be involved in generating outflow resistance.” They state, however, that these mechanisms remain to be defined. 
We would suggest that one excellent candidate for their proposed stretch homeostatic mechanism already has been established. The trabecular meshwork–inducible glucocorticoid response protein (TIGR) is produced by trabecular meshwork cells and then is secreted into the outflow pathway. TIGR proteins/glycoproteins could have potentially important interactions with other components of the juxtacanalicular tissue. 2 3 This region shows a significant concentration of glycoproteins and glycosaminoglycans and is a likely area for outflow resistance. The shear stress response of TIGR was suggested previously on the basis of structural analysis of the TIGR promoter that revealed four putative sequences that predict its response to shear stress. 3 In particular, the TIGR protein is predicted to possess characteristics that could influence outflow resistance in response to stress or other stimuli. Characteristics of the TIGR protein include its oligomerization, specific binding to trabecular meshwork cells, and potential interactions with other extracellular matrix molecules in the trabecular meshwork. 3 Tumminia et al. 1 also suggest that, in glaucoma, these homeostatic mechanisms may be impaired. Changes in TIGR properties due to structural mutations and/or its increased expression could be one of the mechanisms involving outflow obstruction. Several TIGR structure mutations have been confirmed to associate with glaucoma. 4 5 Abnormal stimulation of TIGR gene promoter activity by corticosteroids and oxidative stress were shown to increase TIGR protein expression. 2 Evidence for the overexpression of TIGR in glaucoma comes from the observation that approximately 50% of eyes with open-angle glaucoma show notable increases in TIGR staining in the trabecular meshwork compared with age-matched controls. 6 A sequence variation in the TIGR promoter that segregates with affected members in a large pedigree with primary open-angle glaucoma may also be relevant. 7  
In conclusion, the shear stress response of TIGR suggests that the gene could have a role as a fluid flow regulator. The TIGR gene/protein in its cellular and extracellular forms could serve as a homeostatic stretch response mechanism in the normal eye and play a pathological role in the disease state. Ongoing research should further unravel the biology of this interesting gene. 
San Francisco 
Tumminia SJ, Mitton KP, Arora J, Zelenka P, Epstein DL, Russell P. Mechanical stretch alters the actin cytoskeletal network and signal transduction in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1998;39:1367–1371.
Polansky JR, Fauss DJ, Chen P, et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalmologica. 1997;211:126–139. [CrossRef] [PubMed]
Nguyen TD, Chen P, Huang WD, Chen H, Johnson D, Polansky JR. Gene structure and properties of TIGR, an olfactomedin-related glycoprotein cloned from glucocorticoid-induced trabecular meshwork cells. J Biol Chem. 1998;273:6341–6350. [CrossRef] [PubMed]
Stone EM, Fingert JH, Alward WLW, et al. Identification of a gene that causes primary open angle glaucoma. Science. 1997;275:668–670. [CrossRef] [PubMed]
Adam MF, Belmouden A, Binisti P, et al. Recurrent mutations in a single exon encoding the evolutionary conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. Hum Mol Genet. 1997;6:2091–2097. [CrossRef] [PubMed]
Lutjen–Drecoll E, May CA, Polansky JR, Johnson DH, Bloemendal H, Nguyen TD. Localization of the stress proteins α-B-crystallin and trabecular meshwork inducible glucocorticoid response protein in normal and glaucomatous trabecular meshwork. Invest Ophthalmol Vis Sci. 1998;39:517–525. [PubMed]
Chen H, Chen P, Do TT, et al. Identification of a TIGR promoter sequence variant TIGR.mt1, in a POAG pedigree and estimation of its frequency in adult POAG. [ARVO Abstract]. Invest Ophthalmol Vis Sci. 1998;39(4):S687. Abstract nr 3156.

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