thesoporificmushroom
12/14/09
Dupont Essay Rough Draft
Imagine a life of almost total blindness. This is the struggle many face every day
because of failed attempts to treat ocular surface disorders. In the past, these disorders
were a problem for surgeons and patients and posed a challenge to treat completely.
The most common form of treatment was a complete corneal transplant, replacing the
damaged cornea, the transparent layer in the front of the eye that refracts light, with
healthy corneal tissue from a donor. Patients with diseases that damage the corneal
epithelium, the outer surface of the eye, have impaired vision and compromise the
quality of their life. Those with ocular disorders such as burns and Steven-Johnson
syndrome require this transplant but continue to suffer because of its inefficiency (Tsai
et al., 2000). Corneal transplants have a rejection rate of up to 30 percent, require a
long recovery time and often fail to improve vision (Burman & Sangwan, 2008). Ocular
surface scarring; vascularization, the formation of vessels and capillaries; persistent
epithelial defects and dry eye can persist following a transplant. The integrity of the
corneal epithelium relies upon the existence of limbal stem cells. According to Dua &
Azuara-Blanco (2000), stem cells are essential for cell regeneration and repair and help
maintain homeostasis. They have asymmetric self-renewal, simultaneously replicating
and producing cells with high fidelity; potency; differentiation into different cell
lineages; and slow cell cycling. These properties give them unique opportunities with
regards to ocular surface reconstruction. Pelligrini first used limbal stem cells in sheet
form to treat patients with corneal damage in 1997 (Sullivan & Clynes, 2007). Limbal
stem cell transplants have yielded promising results and are now used to treat ocular
surface disorders by the medical community.
Limbal stem cells are supported by a unique microenvironment called the stem
cell niche. Research by Charukamnoetkanok (2006) supports that the stem cell niche,
named the Palisades of Vogt, protects limbal cells and helps maintain their amazing
properties. Limbal stem cells are classified as “label retaining cells,” meaning that they
have a very slow cell cycling time. They also have asymmetric self-renewal,
simultaneously replicating and producing cells with high fidelity and can differentiate
into different cell lineages. This gives them the property to replace whatever cell type
needs them the most. (Li et al. 2007). Limbal cells have a higher in-vitro proliferative
rate than corneal epithelial cells, making them more effective in corneal transplants
(Pfister, 1994). The corneal epithelium requires constant renewal, the source of this
renewal comes from the limbus. Since many ocular disorders damage the epithelial
surface of the cornea, a limbal transplant will replace damaged cells by differentiating
into corneal epithelial cells after the transplant and thus improving visual acuity.
Scientists have begun exploring the potential of limbal stem cells in corneal
surface reconstruction. Use of autograft, the transplantation of tissue from one part of
the body to another; and allograft, the transplantation of tissue from one person to
another, transplantations of limbal stem cells as an alternative to corneal transplants
are increasing across the world. Autograft transplantations are used in patients with
unilateral ocular damage, damage in only one eye. Limbal cells are taken from the
healthy opposite eye and transplanted into the damaged eye. Limbal stem cells can be
expanded on an amniotic membrane and then transplanted but that isn’t always
required. Amniotic membrane use to expand limbal stem cells in combination with this
procedure allows for more rapid re-epitheliazation and may help prevent infection
(Meller et al., 2002). Allograft transplantations are used in patients with bilateral ocular
damage. Limbal cells are taken from relatives and transplanted into both eyes. Even
though tissue is HLA matched and living donors are preferred, immunosuppressants are
still required following the surgery. Both allograft and autograft surgeries can be
followed by additional ocular surgeries, like keratoplasties, which replace corneal tissue
with healthy tissue from an eye bank, for improved visual clarity. Both procedures have
improved the corneal surface more than and have a shorter follow-up period compared
to standard corneal transplants (Ozdemir et al., 2004).
Research has shown that autograft transplants yield better outcomes than
allograft transplants. In an experiement by Ozdemir et al. (2004), limbal allograft
transplant patients had a follow up period that was 4 months longer than the autograft
patients and only 11% of transplants resulted in functional vision whereas with limbal
autografts it was 80%. The authors also explained how it is more difficult to reduce
corneal vascularization with allograft transplants. Corneal vascularization regressed in all
patients with autograft transplants but only in 4/9 patients who underwent allograft
transplantations. The authors speculate the failure of many allograft transplantations is
due to the advanced stage of ocular surface destruction that the patients in the allograft
group in the experiment had. The rate of rejection is much lower and visual clarity is
higher. They also consider that perhaps the role of allograft transplantations, instead of
to completely treat, should be to stabilize the ocular surface for future surgeries.
Keratoplasties are usually performed 3 months after surgery when the eye surface is
stable. It decreases the risk of corneal graft rejection by controlling inflammation. Many
people do not have a choice between autograft and allograft surgery. Autograft surgery
is only available to those with unilateral ocular surface disorder since the limbal cells
must be derived from the healthy contralateral eye. Allograft surgeries are probably
less effective because the limbal cells are derived from another person.
There have been significant advancements made towards a better
understanding of corneal surface disorders. This has led to the introduction of many
new and effective types of surgery being made available across the globe. Promising
research and studies have shown limbal allograft and limbal autograft surgeries to be
some of the most efficient types to treat ocular surface disorders. By continuing to
explore the vast potential of these limbal stem cells, further uses and applications can
be discovered. The full potential of limbal stem cells and their astonishing healing
properties has yet to be unearthed.
References
Burman, S., & Sangwan, V. (2008). Cultivated Limbal Stem Cell Transplantation for
Ocular Surface Reconstruction. Clinical Ophthalmology, 2(3), 489-502.
Charukamnoetkanok, P. (2006). Corneal Stem Cells: Bridging the Knowledge Gap.
Seminars in Ophthalmology, 21, 1-7.
Dua, H.S., & Azura-Blanco, A. (2000). Limbal Stem Cells of the Corneal Epithelium.
Survey of Opthalmology, 44, 415-425.
Meller, D., Pires, R.T.F., & Tseng, S.C.G. (2002). Ex Vivo Preservation and Expansion of
Human Limbal Epithelial Stem Cells on Amniotic Membrane Cultures. Br J
Ophthalmol, 86, 463-471.
O’ Sullivan, F., & Clynes, M. (2007). Limbal Stem Cells, a Review of their Identification
and Culture for Clinical Use. Cytotechnology, 53(1-3), 101-106.
Ozdemir, O., Tekeli, O., Ornek, K., Arslanpence, A., & Yalcindag, N.F. (2004). Limbal
Autograft and Allograft Transplantations in Patients with Corneal Burns. Eye, 18,
241-248.
Pfister, R.R., (1994). Corneal Stem Cell Disease: Concepts, Categorization, and
Treatment by Auto-and Homotransplantation of Limbal Stem Cells. The Contact
Lens Association of Opthalmologists, 20, 64-72
Tsai, J., Li, L.,& Chen, J. (2000). Reconstruction of Damaged Corneas by
Transplantation of Autologous Limbal Epithelial Cells. The New England Journal
of Medicine, 343, 86-93.
Li,W., Hayashida, Y., Chen, Y., Tseng S. (2007). Niche regulation of corneal epithelial
stem cells at the limbus. Cell Research, 17, 26-36.