The developing ocular lens provides an excellent model system with which to study the intrinsic and extrinsic cues governing cell differentiation. Although the transcription factors Pax6 and Sox2 have been shown to be essential for lens induction, their later roles during lens fiber differentiation remain largely unknown. Using Cre/loxP mutagenesis, we somatically inactivated Pax6 and Sox2 in t...

PURPOSE To determine whether the expression levels and cellular distribution of the facilitative glucose transporters GLUT1 and -3 undergo changes in the hyperglycemic lens. METHODS Hyperglycemia was induced in vivo by injecting rats with streptozotocin or in vitro by culturing lenses in the presence of 50 mM glucose. Northern blot analysis and quantitative RT-PCR were used to detect changes ...

Results of electrical, dye-coupling and morphological studies have previously suggested that gap junctions mediate communication between the anterior epithelium of the lens and the underlying lens fiber cells. This connection is believed to permit 'metabolic cooperation' between these dissimilar cell types and may be of particular importance to the fiber cells, which are thought incapable of au...

SPARC (Secreted Protein, Acidic and Rich in Cysteine) is a matricellular glycoprotein that modulates cell proliferation, adhesion, migration, and extracellular matrix (ECM) production. Although SPARC is generally abundant in embryonic tissues and is diminished in adults, we have found that the expression of SPARC in murine lens persists throughout embryogenesis and adulthood. Our previous studi...

PURPOSE The specific activity of sodium-potassium-adenosine triphosphatase (Na-K-ATPase) in lens fiber cells is lower than the specific activity in lens epithelium. To test whether there is a reduction in the expression of Na-K-ATPase molecules in lens fibers, a Western blot technique was used. METHODS Membrane material was isolated from different regions of the rabbit lens. Na-K-ATPase (aden...

Fibroblast growth factor-2 (FGF2)-mediated signaling plays an important role in fiber cell differentiation in eye lens. We had previously shown that kynurenine (KYN) produced from the overexpression of indoleamine 2,3-dioxygenase (IDO) causes defects in the differentiation of fiber cells, induces fiber cell apoptosis and cataract formation in the mouse lens, and leads to cell cycle arrest in cu...

Little is known about the lipid environment of lens fiber junctions, the plasma membrane structure proposed to be responsible for passage of low molecular weight metabolites between adjacent lens fiber cells. Plasma membranes of the ocular lens are especially rich in fiber junctions. The resistance of junctional domains to disruption by detergent or alkali treatment provides the opportunity to ...

PURPOSE The retinoblastoma (Rb) gene family member p130 binds preferentially to the E2F5 transcription factor and forms a repressive E2F5/p130 complex that inhibits cell cycle progression and tumor growth. It is unclear whether E2F5, either alone or in combination with p130, can interfere with the transcriptional activity of other E2F family members, such as E2F1 and E2F3a, in vivo. In this stu...

Glutathione (GSH), an anionic tripeptide, is the principal antioxidant in the lens where it functions to maintain protein thiols in a reduced state. Levels of GSH are high in both the epithelium and the outer cortex of the lens where the anti-oxidant is synthesized from the amino acids cysteine, glutamate and glycine by g-glutamylcysteinesynthetase and glutathione synthetase. A reducing environ...

The functional roles of bioelectrical signals (ES) created by the flow of specific ions at the mammalian lens equator are poorly understood. We detected that mature, denucleated lens fibers expressed high levels of the α1 and β1 subunits of Na+ /K+ -ATPase (ATP1A1 and ATP1B1 of the sodium pump) and had a hyperpolarized membrane potential difference (Vmem ). In contrast, differentiating, nucleat...