EPITHELIAL STEM CELL AND OCULAR SURFACE TRANSPLANTATION

What is Epithelial Stem Cell and Ocular Surface Transplantation?

Epithelial Stem Cell and Ocular Surface Transplantation refers to the removal of diseased tissue of the cornea and replacing them with healthy tissues that can repopulate ocular surface with healthy cells.

The ocular surface consists of:   • The clear cornea   • The limbus, a 2 to 3mm ring that surrounds the cornea   • The conjunctiva, the surface layer overlying the white portion of the eye (sclera)

What is Ocular Surface Disease (OSD)?

OSD describes a spectrum of conditions resulting in poor healing of the ocular surface. Patients experience chronic red eyes, pain, photophobia, foreign body sensation and poor vision. Common causes include acute chemical burns, extensive recurrent pterygium and Stevens-Johnson Syndrome.

How does stem cell transplantation work?

Stem cells are cells that are "unspecialised" cells that can develop into many different cell types. They occur in all self-renewing tissues of the body. Stem cells can be used to regenerate tissue that has died or is impaired. Stem cells can be applied when corneal diseases affect the tissues of the eye, causing scarring and impairing vision. For the cornea to remain clear, the cornea epithelium must be constantly renewed. Current studies suggest that stem cells located at the limbus are responsible for corneal epithelial renewal and regeneration.

In OSD, the limbal stem cells (LSC) are damaged, leading to limbal stem cell deficiency (LSCD, See Figure 1a, 1b, 1c).

What are the signs of Limbal Stem Cell Deficiency (LSCD)?

The hallmark of end-stage OSD is the formation of an opaque conjunctival sheet of cells on the cornea, causing a disruption of the smooth, clear optical surface (See Fig 1c). Progressive OSD is characterised by chronic inflammation, abnormal blood vessel in growth into the cornea and formation of scars (pannus) (See Figure 1a and 1b).

What are the types of Ocular Surface Reconstructive Surgeries available?
 

The aims of surgery are to remove diseased tissue and replace with healthy stem cell-like tissue that can repopulate the surface with healthy cells.

Amniotic Membrane Transplantation (AMT)  (See Figure 2)

AMT is an established method to treat partial LSCD and rehabilitate poor ocular surface states. AMT is commonly used to treat chemical burns, conjunctival tumor excision, advanced recurrent pterygium, lid fornix reconstruction and persistent corneal epithelial defects (Figure 2a)
 
Limbal Transplantation

Transplantation of LSC tissue using large donor pieces is the traditional and established method of treatment for severe LSCD.
 
a. Autologous (Figure 4): Using the patient’s own healthy cells, the donor limbal tissue from the
   healthy eye is transplanted into the fellow affected eye. This is useful in chemical burns affecting
   only one eye.
 
b. Allograft (Figure 5): Healthy donor limbal tissue taken from a different person or a donor bank
    can be used to replace the affected tissue. In this instance, long-term immunosuppression is
    required to control the risk of immunologic rejection. This method is for very advanced cases of
    LSCD affecting both eyes. 
 
Laboratory-Cultivated Stem Cells for Clinical Transplantation

This is the latest approach to stem cell replacement. Essentially, cells from small donor tissues are grown in the laboratory to propagate stem cells for transplantation. This helps to preserve the donor source. SNEC has a dedicated ocular surface stem cell laboratory at the Singapore Eye Research Institute (SERI) where harvested donor tissue are processed and cultured.

a. Cultured Conjunctival Transplantation (Figure 5)

• This is a SERI-patented method of laboratory cultivation of conjunctival cells on amniotic membrane (AM)
   
• This form of stem cell culture has been useful in providing large pieces of replacement tissue when there is damage/scarring to extensive areas of conjunctiva

b. Cultivated Limbal Transplantation

• This is a laboratory culture of limbal stem cells on AM to reconstruct eyes with total LSCD 
   
• As the cultivation process requires only a small piece of donor tissue, the donor eye is not put at risk for limbal deficiency

c. Cultivated Oral Mucosa Transplantation

• The oral mucosa (mouth lining) has some similar characteristics to the ocular surface cells and may be used to rehabilitate severe LSCD
   
• This is particularly useful for bilateral severe LSCD, when there is no healthy conjunctiva or limbal tissue to harvest.

Fig 1. Signs of LSCD

   
 
Fig. 2 Amniotic membrane transplantation as a patch for deep nonhealing corneal ulceration

    

Fig. 3 Limbal autograph transplant for unilateral LSCD

 
Fig 4. Limbal allograft transplant

 
 
Fig 5. Cultured conjunctival transplantation   

Please visit the following relevant links:

Outcome Results on Corneal & External Eye Disease Procedures
Corneal & External Eye Disease Clinical Staff
I Want an Eye Examination / an Appointment
Care After Corneal Transplant
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Read more on related Eye Conditions and Treatments:

Corneal Infections
Dry Eye
Eye Infections
Pterygium