Normal Development

The formation of the human crystalline lens begins very early in embryogenesis (Fig 3-1).
At approximately 25 days of gestation, 2 lateral evaginations, called the optic vesicles, form
from the forebrain, or diencephalon. As the optic vesicles enlarge and extend laterally,
they become closely apposed and adherent to the surface ectoderm, a single layer of cuboidal
cells, in 2 patches on either side of the head.
Lens Placode
The ectoderm cells that overlie the optic vesicles become columnar at approximately
27 days of gestation. This area of thickened cells is called the lens placode. Growth factors
of the bone morphogenetic protein (BMP) family are required for the formation of the lens
placode and for subsequent lens formation.
Lens Pit
The lens pit appears at 29 days of gestation as an indentation (infolding) of the lens placode.
The lens pit deepens and invaginates to form the lens vesicle.
Lens Vesicle
As the lens pit continues to invaginate, the stalk of cells connecting it to the surface ectoderm
degenerates by programmed cell death (apoptosis), thereby separating the lens cells
from the surface ectoderm. The resultant sphere, a single layer of cuboidal cells encased in
a basement membrane (the lens capsule), is called the lens vesicle. At the time of its formation
at 30 days' gestation, the lens vesicle is approximately 0.2 mm in diameter.
Because the lens vesicle was formed through a process of invagination of the surface
ectoderm, the apices of the cuboidal cells are oriented toward the lumen of the lens vesicle,
with the base of each cell attached to the capsule around the periphery of the vesicle. At
the same time that the lens vesicle is forming, the optic vesicle is invaginating to form the
2-layered optic cup.

Primary Lens Fibers and the Embryonic Nucleus

The cells in the posterior layer of the lens vesicle stop dividing and begin to elongate. As
they elongate, they begin to fill the lumen of the lens vesicle. At approximately 40 days of
gestation, the lumen of the lens vesicle is obliterated. The elongated cells are called the
primary lens fibers. As the fiber cells mature, their nuclei and other membrane-bound
organelles undergo degradation, a process that reduces light scattering. The primary lens
fibers make up the embryonic nucleus that will ultimately occupy the central area of the
lens in adult life. The cells of the anterior lens vesicle remain as a monolayer of cuboidal cells, the lens
epithelium. Subsequent growth of the lens is due to proliferation within the epithelium.
The lens capsule develops as a basement membrane elaborated by the lens epithelium anteriorly
and by lens fibers posteriorly. Pooyan 66961526-7
Secondary Lens Fibers
After they proliferate, the epithelial cells near the lens equator elongate to form secondary
lens fibers. The anterior aspect of each developing lens fiber extends anteriorly beneath
the lens epithelium, toward the anterior pole of the lens. The posterior aspect of each developing lens fiber
extends posteriorly along the capsule, toward the posterior pole of
the lens. In this manner, new lens fibers are continually formed, layer upon layer. As each
secondary fiber cell detaches from the capsule, it loses its nucleus and membrane-bound
organelles. The secondary lens fibers formed between 2 and 8 months of gestation make
up the fetal nucleus.
Lens Sutures and the Fetal Nucleus
As lens fibers grow anteriorly and posteriorly, a pattern emerges where the ends of the
fibers meet and interdigitate with the ends of fibers arising on the opposite side of the
lens, near the anterior and posterior poles. These patterns of cell association are known
as sutures. Y-shaped sutures are recognizable at about 8 weeks of gestation, with an erect
Y-suture appearing anteriorly and an inverted Y-suture posteriorly (Fig 3-2). As the lens
fibers continue to form and the lens continues to grow, the pattern oflens sutures becomes
increasingly complex, resulting in 12 or more suture branches in the adult eye. The influences
responsible for the precise formation and changing organization of the suture pattern
remain a mystery.
The human lens weighs approximately 90 mg at birth, and it increases in mass at the
rate of about 2 mg per year as new fibers form throughout life. The central, or oldest, lens process progressively
reduces the amplitude of accommodation.
Tunica Vasculosa Lentis
At about 1 month of gestation, the hyaloid artery, which enters the eye at the optic disc,
branches to form a network of capillaries, the tunica vasculosa lentis, on the posterior
surface of the lens capsule (Fig 3-3). These capillaries grow toward the equator of the
lens, where they anastomose with a second network of capillaries, called the anterior
pupillary membrane, which derives from the ciliary veins and which covers the anterior
surface of the lens. At approximately 9 weeks' gestation, the capillary network surrounding
the lens is fully developed; it disappears by an orderly process of programmed cell
death shortly before birth. Sometimes a remnant of the tunica vasculosa lentis persists
as a small opacity or strand, called a Mittendorf dot (discussed later), on the posterior
aspect of the lens. In other eyes, remnants of the pupillary membrane are often visible as
pupillary strands.
Zonules of Zinn
Experimental evidence suggests that the zonular fibers are secreted by the ciliary epithelium,
although how these fibers insert into the lens capsule is not known. The zonular
fibers begin to develop at the end of the third month of gestation.