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Publication : Cochlin, intraocular pressure regulation and mechanosensing.

First Author  Goel M Year  2012
Journal  PLoS One Volume  7
Issue  4 Pages  e34309
PubMed ID  22496787 Mgi Jnum  J:224196
Mgi Id  MGI:5661656 Doi  10.1371/journal.pone.0034309
Citation  Goel M, et al. (2012) Cochlin, intraocular pressure regulation and mechanosensing. PLoS One 7(4):e34309
abstractText  Fluid shear modulates many biological properties. How shear mechanosensing occurs in the extracellular matrix (ECM) and is transduced into cytoskeletal change remains unknown. Cochlin is an ECM protein of unknown function. Our investigation using a comprehensive spectrum of cutting-edge techniques has resulted in following major findings: (1) over-expression and down-regulation of cochlin increase and decrease intraocular pressure (IOP), respectively. The overexpression was achieved in DBA/2J-Gpnmb(+)/SjJ using lentiviral vectors, down-regulation was achieved in glaucomatous DBA/2J mice using targeted disruption (cochlin-null mice) and also using lentiviral vector mediated shRNA against cochlin coding region; (2) reintroduction of cochlin in cochlin-null mice increases IOP; (3) injection of exogenous cochlin also increased IOP; (4) increasing perfusion rates increased cochlin multimerization, which reduced the rate of cochlin proteolysis by trypsin and proteinase K; The cochlin multimerization in response to shear stress suggests its potential mechanosensing. Taken together with previous studies, we show cochlin is involved in regulation of intraocular pressure in DBA/2J potentially through mechanosensing of the shear stress.
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