Cochlin in the eye: functional implications

Renata Picciani,¹ Kavita Desai,¹ Jasenka Guduric-Fuchs,² Tiziana Cogliati,² Cynthia C. Morton,³ and Sanjoy K. Bhattacharya¹*, Prog Retin Eye Res. 2007 September; 26(5): 453–469.

1Bascom Palmer Eye Institute, University of Miami, Miami, Florida, 33136
2Centre for Vision Sciences, Queen's University School of Biomedical Sciences, BELFAST BT12 6BA, UK
3Harvard Medical School, Brigham and Women's Hospital New Research Building, Room 160D, 77 Avenue Louis Pasteur, Boston, MA 02115

*Corresponding Author McKnight Vision Research Building, Bascom Palmer Eye Institute, University of Miami, 1638 NW 10th Avenue, Room 706A, Miami, Florida 33136, Tel: 305-482-4103, Fax: 305-326-6547, Email: Sbhattacharya@med.miami.edu

Abstract

Aqueous humor is actively produced in the ciliary epithelium of the anterior chamber and has important functions for the eye. Under normal physiological conditions, the inflow and outflow of the aqueous humor are tightly regulated, but in the pathologic state this balance is lost. Aqueous outflow involves structures of the anterior chamber and experiences most resistance at the level of the trabecular meshwork (TM) that acts as a filter. The modulation of the TM structure regulates the filter and its mechanism remains poorly understood. Proteomic analyses have identified cochlin, a protein of poorly understood function, in the glaucomatous TM but not in healthy control TM from human cadaver eyes. The presence of cochlin has subsequently been confirmed by Western and immunohistochemical analyses. Functionally, cochlin undergoes multimerization induced by shear stress and other changes in the microenvironment. Cochlin along with mucopolysaccharide deposits have been found in the TM of glaucoma patients and in the inner ear of subjects affected by the hearing disorder DNFA9, a late onset, progressive disease that also involves alterations in fluid shear regimes. In vitro, cochlin induces aggregation of primary TM cells suggesting a role in cell adhesion, possibly in mechanosensation, and in modulation of the TM filter.