Abstract
The avascular eye lens generates its own microcirculation that is required for maintaining lifelong lens transparency. The microcirculation relies on sodium ion flux, an extensive network of gap junction (GJ) plaques between lens fiber cells and transmembrane water channels. Disruption of connexin proteins, the building blocks of GJs, or aquaporins, which make up water and adhesion channels, lead to lens opacification or cataracts. Recent studies have revealed that disruption of Eph-ephrin signaling, in particular the receptor EphA2 and the ligand ephrin-A5, in humans and mice lead to congenital and age-related cataracts. We investigated whether changes in lens transparency in EphA2 or ephrin-A5 knockout (–/–) mice is related to changes in GJ coupling and lens fluid and ion homeostasis. Immunostaining revealed changes in connexin 50 (Cx50) subcellular localization in EphA2–/– peripheral lens fibers and alteration in aquaporin 0 (Aqp0) staining patterns in ephrin-A5–/– and EphA2–/– inner mature fiber cells. Surprisingly, there was no obvious change in GJ coupling in knockout lenses. However, there were changes in fiber cell membrane conductance and intracellular voltage in knockout lenses from 3-month-old mice. These knockout lenses displayed decreased conductance of mature fiber membranes and were hyperpolarized compared to control lenses. This is the first demonstration that the membrane conductance of lens fibers can be regulated. Together these data suggest that EphA2 may be needed for normal Cx50 localization to the cell membrane and that conductance of lens fiber cells requires normal Eph-ephrin signaling and water channel localization.
Highlights
The eye lens is a transparent, avascular, and ellipsoidal tissue in the anterior segment of the eye
Since mild nuclear cataracts are often present in EphA2−/− lenses, we evaluated the localization of Cx46, connexin 50 (Cx50), and aquaporin 0 (Aqp0) by performing immunostaining in 6-week-old control, ephrin-A5−/− and EphA2−/− lens frozen sections
Ephrin-A5−/− lenses were evaluated in this study as a comparison for EphA2−/− lenses and to learn more about whether these two molecules interact in subpopulations of cells in the lens
Summary
The eye lens is a transparent, avascular, and ellipsoidal tissue in the anterior segment of the eye. The bulk of the lens is composed of elongated fiber cells that are covered by a monolayer of epithelial cells covering the anterior hemisphere. Epithelial cells near the lens equator proliferate and differentiate into new generations of fiber cells, and the continuous addition of fiber cells cause life-long growth of the lens (Bassnett, 2002; Lovicu and Robinson, 2004). Lens fiber cells are connected by a network of large gap junction (GJ) plaques (Gong et al, 1997; Rong et al, 2002; Mathias et al, 2010; Cheng et al, 2015). The avascular lens is hypothesized to be supported by a microcirculation with an inward
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