Biomedical Engineering Reference
In-Depth Information
colleagues have described another limbal epithelial crypt structure as distinct
anatomical extensions from the peripheral aspect of the limbal palisades [
25
].
These structures are thought to be larger in size but fewer in number than the
limbal crypts described by Shortt. The focal stromal projections are finger-like
projections of stroma extending upward into the corneal limbal epithelium. They
are surrounded by small, tightly packed cells and contain a central blood vessel.
There is regional variability in the distribution of the limbal crypts as they are
predominant at the superior and inferior aspects of the corneal circumference,
where the eyelids may offer added physical protection from ultraviolet light. The
close proximity of the limbal cells in crypts to a vascular supply suggests an
important niche feature likely to be providing nutrients and survival factors.
Equally, the juxtaposition of keratocytes to LESCs is in keeping with the concept
of cell-cell interactions playing an important role in maintenance of a stem cell
population (Fig.
3.1
f). This theory is supported by recent research using an in vitro
3D tissue model of the ocular surface and underlying stroma which suggests that if
limbal epithelial cells are closely associated with keratocytes, as in vivo, the newly
seeded epithelial layer becomes more organised and the production of basement
membrane proteins is increased [
26
].
3.5 Limbal Stem Cell Deficiency
With regards to maintenance of a normal corneal epithelium, the main functions of
the limbus are to harbour stem cells that replenish the corneal epithelium, and to
act as a physical barrier separating the corneal epithelium and the phenotypically
very different conjunctival epithelium and its underlying blood vessels [
27
,
28
].
When these two functions of the limbus fail, the disease of LESC deficiency
results. In this disease, due to a deficiency of the LESCs, the corneal epithelium
cannot be renewed normally, and persistent and recurrent corneal epithelial defects
occur [
29
]. In addition, the limbal barrier effect fails and the conjunctival epi-
thelium and its underlying blood vessels encroach on to the normally avascular
corneal surface to replace the failing or deficient corneal epithelium (Fig.
3.1
g).
The result is a disease, which is both painful and visually debilitating.
3.6 Causes of Limbal Stem Cell Deficiency
There are many causes of LESC deficiency [
30
]. In all however, the result is an
unstable and conjunctivalised corneal surface. LESC deficiency essentially results
from a primary loss of the numbers of limbal stem cells or a dysfunction of the
limbal stem cells, either as a result of the stem cell itself being dysfunctional or
from the microenvironment being abnormal which causes the stem cell dysfunc-
tion. The causes of LESC deficiency can be separated into primary or hereditary
