The lens is composed of numerous sheets of slender fiber cells covered by a monolayer of epithelium at its anterior surface. The lens permits incident light to pass through and helps to form a focused image on the retina through the mechanism of accommodation. The lens possesses several unique features serving these specific functions. It contains a high concentration of transparent crystallin proteins which increase the refractive index. The lens has no blood supply and its mature fiber cells lose their organelles during the maturation process to eliminate light scattering. Metabolic activities in the lens are low and proceed anaerobically and the exchanges of ions and small metabolites between lens cells depend on gap junctions. Gap junctions between lens fiber cells exhibit unique structural and physiological characteristics in different lens regions. Gap junctions in the superficial differentiating fiber zone are pH sensitive while those in the deeper mature fiber zone are pH insensitive. Since the fiber cell cytoplasm is significantly more acidic (pH 6.81) deep in the lens, the loss of gap junction sensitivity to pH is crucial to lens survival. Biochemical and molecular studies have identified two gap junction proteins (connexins), Cx46 and Cx50, in the lens fibers. The COOH-terminal domain of the connexin molecule is a site for protein binding and phosphorylation by kinases that directly regulate channel gating. The loss of the COOH-terminus of Cx50 in the lens has been suggested to be responsible for its pH sensitivity change, and may be crucial to keeping the gap junction channel open for mature fiber cell survival in the adult lenses.
In addition, lens fibers require an elaborate interlocking system for maintaining their structural order and stability which are crucial for lens transparency especially during the deformation which accompanies visual accommodation. Interlocking connections between lens fibers exhibit many different configurations and are basically in the forms of ball-and-sockets, protrusions and tongue-and-grooves in various species studied. Most interestingly, the tongue-and-groove domain has been shown to be associated with square array junctions which are formed by aquaporin 0 protein. Our lab will test the hypothesis that aquaporin 0 serves a dual role as water channel and cell-cell adhesion during fiber cell differentiation and maturation.
- NIH/NEI R01 grant EY05314-23 (PI) (9/1/2007 -- 8/31/2012) " Cell Junctions and Cell Membranes in the Lens
- NIH/NEI R01 grant EY019012-01 (Subcontract) (7/1/2009 – 6/30/2014) "Regulation of Lens Fiber Cell Organization"
Research Key Words: Cataracts, lens, electron microscopy