To understand the structural organization responsible for lens function, we
have studied the three-dimensional arrangement of cells in the lens, and t
he 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 pore to form the cortex, and fold inward at t
he posterior pole to form the nucleus. The basal surfaces of all cells of t
he cortex (approximately two thirds of all lens cells) are bathed by the aq
ueous and Vitreous humors, Therefore, their metabolism is not limited by di
ffusion of nutrients into the avascular lens. The apical surfaces of all co
rtical 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 anteri
or pole, and is formed by the association of the apical surface of anterior
cortical cells and the apical surface of cortical fibers extending from th
e posterior pore, The modiolus is located close to the equator at the later
al edge of the apical interface, and is formed by the tapered apical ends o
f equatorial cortical fibers. The plasma membrane of cortical cells at the
anterior pole are connected through 'leaky' tight junctions and small gap j
unctions. Extensive gap junction plaques composed of connexin43 connect equ
atorial fibers at the modiolus and posterior cortical fibers at the apical
interface. Single cell-to-cell channels composed of connexin46 and connexin
50 connect the lateral surfaces of equatorial and posterior cortical fibers
. The lateral surfaces of these fibers also contain extensive junctions com
posed of aquaporin-0, The nucleus is connected to the humors through the pa
racellular pathway represented by the anterior (apical) and posterior (basa
l) 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 e
xtensive wavy junctions composed of aquaporin-0, probably for the control o
f the permeability of the paracellular pathway. We propose a simple epithel
ium 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 p
laques composed of connexin43 at the apical surface. and single or small pl
aques of cell-to-cell channels composed of connexin46 and connexin50 in the
lateral surfaces. (C) 2000 Academic Press.