BrightMEM Scientific Background

A sample of content in this file:

Significance of Research Question/Purpose:
Limbal stem cell deficiency (LSCD) is a devastating disease that accounts
for an estimated 15-20% of corneal blindness worldwide.1 This disease
results from loss or dysfunction of LSCs, a population of pluripotent cells
that continuously regenerates the transparent epithelium of the cornea
throughout life.2–4 LSCs are found on the ocular surface in the limbus, where
they divide and differentiate into transient amplifying cells (TAC), which then
migrate centripetally across the cornea and further differentiate into mature
corneal epithelium.5 Loss of these cells from chemical burns, autoimmune
diseases, various congenital disorders, ocular surgeries, and other surface
insults can result in partial or total LSCD and associated vision loss.2
Without a healthy population of LSCs to regenerate the corneal epithelium,
LSCD patients are at risk for recurrent erosions, persistent epithelial defects
(PED), corneal conjunctivalization, corneal scarring, and corneal melting.
Standard corneal transplants are ineffective. Instead, transplantation of
donor limbal tissue containing donor LSCs (keratolimbal allografts or KLAL)
is often necessary. However, because systemic immunosuppression with
prednisone, mycophenolate, and tacrolimus is required to prevent rejection
of the highly antigenic limbal grafts, KLAL is almost always reserved for only
the most severe cases.6-8 For many patients, the risks associated with
immunosuppression outweigh the benefits of treatment. Artificial corneas
made from plastic polymers such as the Boston keratoprosthesis (KPro)
have also been used to treat LSCD because their ability to remain clear in
the absence of LSCs and healthy corneal epithelium;9 however, the
significant rates of glaucoma, corneal melt, implant extrusion, infectious
keratitis, and endophthalmitis associated with KPros have also limited their
use in mild to moderate disease.10 As such, current treatment options for
LSCD remain limited.