The cornea is the transparent, dome-shaped outer layer at the front of the eye. It serves as the eye’s primary window, allowing light to enter and providing approximately two-thirds of the eye’s focusing power. To maintain clarity and function, the cornea’s outermost layer, the epithelium, must be continuously renewed and repaired. This constant maintenance is managed by specialized stem cells, which possess the unique ability to both self-renew and differentiate, giving rise to all the mature cells needed for the tissue.
The Cornea’s Self-Repair System
The corneal epithelium acts as a protective barrier and undergoes constant turnover, with older or damaged cells shedding from the surface. This continuous renewal cycle is powered by epithelial stem cells located at the peripheral edge of the cornea, known as the limbus. The limbus forms the transitional border between the clear cornea and the white outer layer of the eye, the sclera.
Limbal stem cells maintain the corneal surface by producing transient amplifying cells. These daughter cells divide rapidly before maturing into the final corneal epithelial cells, ensuring a continuous supply of fresh cells.
The newly generated cells migrate across the cornea in a highly organized pattern known as centripetal movement. They travel inward from the limbus toward the central cornea, where they differentiate into the final surface cells. This constant, inward flow replaces the cells naturally shed, ensuring the corneal surface remains smooth and transparent.
Understanding Vision Loss Due to Stem Cell Failure
When the limbal stem cell population is destroyed or dysfunctional, the cornea’s self-repair system fails, leading to Limbal Stem Cell Deficiency (LSCD). This failure is often caused by severe external trauma, such as chemical or thermal burns, which obliterate the limbal tissue. LSCD can also result from systemic inflammatory diseases like Stevens-Johnson Syndrome or ocular cicatricial pemphigoid, which prevent the stem cells from functioning.
Without healthy limbal stem cells, the neighboring conjunctival tissue begins to invade the cornea. This invasion, called conjunctivalization, introduces blood vessels and opaque, scar-like tissue onto the clear cornea. The presence of these features scatters light, resulting in significant vision impairment and opacity.
Patients with LSCD experience chronic symptoms, including persistent pain, inflammation, and recurrent breakdowns of the corneal epithelium. The damaged surface is unstable and prone to ulceration, increasing discomfort and the risk of infection. Traditional corneal transplantation is ineffective because the new graft quickly fails without a functional stem cell population to maintain its epithelium.
Clinical Restoration of the Cornea
Restoring vision in LSCD patients requires surgically reintroducing a healthy source of limbal stem cells through Limbal Stem Cell Transplantation (LSCT). This intervention targets the root cause—the absence of progenitor cells—by providing a new reservoir capable of self-renewal and differentiation. The transplanted stem cells integrate into the recipient’s limbal niche, rebuilding the system that maintains the corneal surface.
Once established, the new stem cells generate transient amplifying cells. These cells migrate centripetally, pushing out the invading conjunctival tissue and repopulating the cornea with a transparent epithelial layer. This repopulation restores the cornea’s anatomical success, characterized by a smooth, stable, and avascular surface.
The restoration of a clear, non-vascularized epithelial surface directly leads to improved vision. By eliminating scar tissue and invading blood vessels, the cornea regains its transparency. This allows light to pass through the eye unimpeded and focus correctly onto the retina, reversing the pathological changes of LSCD.
Methods of Stem Cell Transplantation
The choice of transplantation technique depends on whether the patient has one healthy eye or if both eyes are affected. When LSCD affects only one eye, the preferred method is an autologous transplant, harvesting stem cells from the patient’s own healthy eye. This approach eliminates the risk of immunological rejection, avoiding the need for long-term immunosuppression.
Autologous Techniques (One Eye Affected)
One common technique is Simple Limbal Epithelial Transplantation (SLET). This involves taking a small biopsy from the healthy limbus, dividing it into fragments, and placing them directly onto the diseased cornea. Another method is Cultivated Limbal Epithelial Transplantation (CLET), where a tiny biopsy is taken and the stem cells are grown in a laboratory to expand their number. The cultivated cell sheet is then transplanted, minimizing the tissue harvested from the donor eye.
Allogeneic Techniques (Both Eyes Affected)
If LSCD affects both eyes, an autologous source is unavailable, necessitating an allogeneic transplant using donor tissue from a living-related donor or a cadaveric source. Since the cells are not genetically matched, allogeneic transplants require the patient to take systemic immunosuppressive medication to prevent rejection. Research is exploring alternative sources, such as cultivating epithelial cells from the patient’s own oral mucosa, as a potential autologous option for bilateral cases.