Cochlin, intraocular pressure regulation and mechanosensing

Manik Goel, Adam E. Sienkiewicz, Renata Picciani, Jianhua Wang, Richard K Lee, Sanjoy K Bhattacharya

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere34309
JournalPLoS One
Volume7
Issue number4
DOIs
StatePublished - Apr 4 2012

Fingerprint

Pressure regulation
Intraocular Pressure
shear stress
extracellular matrix
Shear stress
mice
Down-Regulation
Proteolysis
Endopeptidase K
Inbred DBA Mouse
Extracellular Matrix Proteins
proteolysis
Trypsin
trypsin
Small Interfering RNA
Extracellular Matrix
Perfusion
injection
Injections
Fluids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cochlin, intraocular pressure regulation and mechanosensing. / Goel, Manik; Sienkiewicz, Adam E.; Picciani, Renata; Wang, Jianhua; Lee, Richard K; Bhattacharya, Sanjoy K.

In: PLoS One, Vol. 7, No. 4, e34309, 04.04.2012.

Research output: Contribution to journalArticle

Goel, Manik ; Sienkiewicz, Adam E. ; Picciani, Renata ; Wang, Jianhua ; Lee, Richard K ; Bhattacharya, Sanjoy K. / Cochlin, intraocular pressure regulation and mechanosensing. In: PLoS One. 2012 ; Vol. 7, No. 4.
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