Limbal stem cells maintain the cornea, the transparent outer layer of the eye. These cells are responsible for the continuous renewal and repair of the corneal surface. The loss of these cells can lead to a condition that compromises sight, making it important to understand their biology and potential therapies.
Understanding Limbal Stem Cells and Their Function
Limbal stem cells (LSCs) can self-renew and differentiate into other cell types. LSCs produce transient amplifying cells which then become the mature epithelial cells of the cornea. This constant supply of new cells replenishes the corneal surface as it is exposed to the environment.
These cells reside in a niche at the border between the cornea and the white sclera, a region called the limbus. The limbus contains structures like the Palisades of Vogt, which are small ridges that house and protect the LSCs. This niche provides the signals and support needed to maintain the stem cell population throughout life.
The primary function of LSCs is to sustain the corneal epithelium. They act as a continuous source for new epithelial cells, which migrate from the limbus to the center of the cornea to replace old or damaged cells. This process is for routine tissue maintenance and for healing after an injury, such as a scratch or abrasion.
A secondary function of LSCs is to act as a barrier. This barrier prevents the conjunctiva, the mucous membrane covering the front of the eye, from growing over the corneal surface. Without this barrier, the cornea would lose its transparency, leading to a reduction in vision.
When Limbal Stem Cells Fail: Deficiency and Its Impact
Limbal Stem Cell Deficiency (LSCD) arises when the LSC population is depleted or impaired, which can be partial or complete. The causes are either acquired or genetic. Acquired causes are more common and include chemical burns, chronic inflammation, infections, or long-term contact lens use. Rarer genetic causes include conditions like aniridia.
The failure of LSCs disrupts corneal regeneration, leading to several symptoms. Patients experience chronic pain, a persistent foreign body sensation, light sensitivity (photophobia), and blurred vision. The eye may appear chronically red and inflamed because the corneal surface cannot heal properly, leading to recurrent erosions.
Without a functional LSC barrier, the conjunctival epithelium encroaches upon the corneal surface, a process called conjunctivalization. This causes new blood vessel growth (neovascularization) and a loss of transparency (opacification), leading to progressive scarring and a severe decline in vision. Diagnosis involves a clinical examination looking for signs like an irregular corneal surface and the presence of goblet cells on the cornea.
Restoring Vision: Therapeutic Approaches for LSCD
The goal of treating LSCD is to replenish the stem cell population and restore a clear corneal surface. Treatment involves transplanting healthy limbal stem cells to the affected eye. The source of these cells determines the transplant type: autologous (from the patient) or allogeneic (from a donor).
For LSCD in one eye, an autologous transplant is preferred. A small piece of limbal tissue is harvested from the healthy eye and grafted onto the damaged one. This approach eliminates the risk of immune rejection, so long-term immunosuppressive medication is not required.
When both eyes are affected, an allogeneic transplant is necessary, using tissue from a living or deceased donor. This approach introduces the risk of immune rejection, where the recipient’s immune system attacks the donor cells. To prevent this, patients must take long-term systemic immunosuppressive drugs, which have potential side effects.
Innovations in Limbal Stem Cell Transplantation
Advanced techniques for LSC transplantation improve success rates and minimize risks. One method is Cultivated Limbal Epithelial Transplantation (CLET), which involves harvesting a small limbal biopsy. LSCs are isolated from the biopsy, expanded in a lab, and grown on a carrier membrane that is then transplanted onto the patient’s eye.
CLET requires much less donor tissue than traditional grafting, reducing the risk to a healthy donor eye. This method has high success rates with outcomes comparable to direct limbal transplantation. It is valuable for unilateral LSCD, preserving the healthy eye while providing enough cells to restore the damaged one.
Another technique is Simple Limbal Epithelial Transplantation (SLET), which avoids laboratory cultivation, making it more accessible and less costly than CLET. In SLET, a small limbal biopsy is cut into smaller pieces and distributed onto a carrier membrane over the damaged cornea. The stem cells then migrate from these fragments to repopulate the ocular surface.
Research into alternative cell sources is also underway. Scientists are exploring induced pluripotent stem cells (iPSCs), which can be generated from a patient’s own skin or blood cells. These iPSCs can be programmed to become LSCs, providing a personalized source of stem cells and eliminating the need for donor tissue.