Cochlin in the eye: Functional implications

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.

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

“…These studies examined only POAG samples and could not demonstrate differences observed in other forms of glaucoma. Other reports found the presence of type IV collagen in the TM and SC (Kizhatil et al, 2014; Picciani et al, 2007a; Picciani et al, 2007b). Prior ultrastructure studies demonstrated the accumulation of BM-like material staining for type IV collagen in steroid-induced glaucoma.…”

Extralabyrinthine Manifestations of DFNA9

“…The mechanism by which cartilage-like deposits develop within the middle ear is unknown. Although cochlin was initially discovered within the inner ear, it has since been reported to be widely expressed in multiple organs including the spleen, brain, kidneys, testis, uterus, intestine, and eye, among others (Robertson et al 1994;Rodriguez et al 2004;Picciani et al 2007). The middle ear has yet to be specifically evaluated for cochlin expression.…”

“…However, additional data exists that suggests cochlin may truly play a role in ocular disease. Proteomic studies have demonstrated differential expression of cochlin within the trabecular meshwork of glaucomatous patients (Picciani et al 2007;Picciani et al 2009). These ophthalmologic findings along with evidence from this study showing histopathologic changes within the middle ear demonstrate that the effects of cochlin-related disease are not solely limited to the inner ear.…”

The CAP Superfamily: Cysteine-Rich Secretory Proteins, Antigen 5, and Pathogenesis-Related 1 Proteins—Roles in Reproduction, Cancer, and Immune Defense

“…LCCL domains are found in potential complement factors in the case of limulus factor C and the Plasmodium Scavenger Receptor Cysteine-Rich, LCCL, Adhesive-like Protein (PSLAP) (165,168), in the human deafness associated gene (169 -173), in akhirin (and cochlin), which have been implicated in eye development (167,174,175), and also within CAPLD2. It has been proposed that proteins containing LCCL domains may be involved in cellular adhesion (167,168), although it is not known whether this is associated with the LCCL domain specifically or with sequences.…”