Epithelial organization of the mammalian lens.

To understand the structural organization responsible for lens function, we have studied the three-dimensional arrangement of cells in the lens, and the location and molecular composition of specialized junctions controlling the paracellular and transcellular pathways. The lens is formed by a single layer of polarized cells that elongate along their apical-basal axis from the anterior to the posterior pole to form the cortex, and fold inward at the posterior pole to form the nucleus. The basal surfaces of all cells of the cortex (approximately two thirds of all lens cells) are bathed by the aqueous and vitreous humors. Therefore, their metabolism is not limited by diffusion of nutrients into the avascular lens. The apical surfaces of all cortical fibers are directed toward the interior of the lens, where they form two distinct structures here referred to as the 'apical interface' and the 'modiolus'. The apical interface is located at a point close to the anterior pole, and is formed by the association of the apical surface of anterior cortical cells and the apical surface of cortical fibers extending from the posterior pole. The modiolus is located close to the equator at the lateral edge of the apical interface, and is formed by the tapered apical ends of equatorial cortical fibers. The plasma membrane of cortical cells at the anterior pole are connected through 'leaky' tight junctions and small gap junctions. Extensive gap junction plaques composed of connexin43 connect equatorial fibers at the modiolus and posterior cortical fibers at the apical interface. Single cell-to-cell channels composed of connexin46 and connexin50 connect the lateral surfaces of equatorial and posterior cortical fibers. The lateral surfaces of these fibers also contain extensive junctions composed of aquaporin-0. The nucleus is connected to the humors through the paracellular pathway represented by the anterior (apical) and posterior (basal) suture lines. Therefore, the metabolic needs of nuclear fibers cannot be fulfilled by simple diffusion and requires the cell-to-cell pathway formed by specialized junctions. The lateral surfaces of nuclear fibers contain extensive wavy junctions composed of aquaporin-0, probably for the control of the permeability of the paracellular pathway. We propose a simple epithelium model for the lens in which nutrients move into the nucleus through the paracellular pathway represented principally by the suture lines, and the transcellular pathway represented by an extensive network of gap junction plaques composed of connexin43 at the apical surface, and single or small plaques of cell-to-cell channels composed of connexin46 and connexin50 in the lateral surfaces. Copyright 2000 Academic Press.