The lens epithelium: Focus on the expression and function of the α-crystallin chaperones

Abstract

Lens epithelial cells are the parental cells responsible for growth and development of the transparent ocular lens. Many elegant investigations into their biology have focused on the factors that initiate and regulate lens epithelial cell differentiation. Because they serve key transport and cell maintenance functions throughout life, and are the primary source of metabolic activity in the lens, mechanisms to maintain lens epithelial cell integrity and survival are critical for lens transparency. The molecular chaperones α-crystallins are abundant proteins synthesized in the differentiated lens fiber cell cytoplasm. However, their expression in lens epithelial cells has only been appreciated very recently. Besides their important roles in the refractive and light focusing properties of the lens, α-crystallins have been implicated in a number of non-refractive pathways including those involving stress response, apoptosis and cell survival. The most convincing evidence for their importance in the lens epithelium has been shown by studies on the properties of lens epithelial cells from αA and αB-crystallin gene knockout mice. The effective combination of genetics, cell and molecular biology possible with lens epithelial cells is attracting an increasing number of researchers focused on understanding how lens epithelial cells coordinate survival, proliferation and differentiation. Cell facts• Lens epithelial cells are responsible for the growth and development of the entire ocular lens • Lens development is controlled by cell cycle regulators, signaling molecules and growth factors such as FGF • Lens epithelial cells express members of the small heat shock protein family of molecular chaperones, αA and βB-crystallins, the first crystallins to be expressed during lens development • α-Crystallins likely protect lens epithelial cells from environmental stress throughout life, and thus may delay the onset of age-related cataract • Lens epithelial cell proliferation is deregulated in posterior capsule opacification leading to secondary cataract, a complication in up to 50% of cataract surgeries Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

Chaperone Peptides of α-Crystallin Inhibit Epithelial Cell Apoptosis, Protein Insolubilization, and Opacification in Experimental Cataracts

“…Measurement of Apoptosis-Human lens epithelial cells (HLE) 2 were isolated from the lens of a 44-year-old donor and cultured in DMEM supplemented with 10% FBS as previously described for mouse lens epithelial cells (27). Cells between passages 5 and 6 were used for the experiments.…”

“…It is composed of two subunits, ␣A and ␣B, whose sequences show significant homology to each other and to other small heatshock proteins (1). The ␣A-and ␣B-crystallin heteropolymers are present in the lens as polydisperse oligomers with an average molecular mass of 800 kDa (2,3). ␣A-Crystallin is present mainly in the lens, whereas ␣B-crystallin, in addition to the lens, is present in several other tissues, including the retina, heart, and kidney (4,5).…”

Oxidative Stress, Lens Gap Junctions, and Cataracts

“…However, the lens contains several nonenzymatic and enzymatic mechanisms to protect itself from oxidative stress and to repair oxidatively damaged cell components. The nonenzymatic mechanisms include the presence of high concentrations of ascorbate, reduced glutathione (GSH), crystallins (which act as protein chaperones), and free UV filters (e.g., tryptophan derivatives in the human lens and NAD(P)H in rabbit, guinea pig and frog lenses (2,16,125,127).…”

The Common Modification in αA-Crystallin in the Lens, N101D, Is Associated with Increased Opacity in a Mouse Model

“…The ocular lens has a unique cellular architecture consisting of a single layer of cuboidal epithelial cells, which divide and differentiate at the equator into fiber cells (1). The fiber cells elongate, and they synthesize fiber cell-specific proteins, such as AQP0 (aquaporin-0)/MIP (main intrinsic protein), cytoskeletal proteins, and crystallins (1)(2)(3)(4).…”

“…The fiber cells elongate, and they synthesize fiber cell-specific proteins, such as AQP0 (aquaporin-0)/MIP (main intrinsic protein), cytoskeletal proteins, and crystallins (1)(2)(3)(4). As the new fiber cells are laid down at the lens equator, the older fiber cells are pushed toward the lens core and simultaneously lose their nuclei and organelles while exhibiting very little protein turnover.…”