Download thesoporificmushroom 12/14/09 Dupont Essay Rough Draft Imagine

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 the failed attempts to treat ocular surface disorders. In the past, these
disorders were a huge 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 with healthy corneal tissue from a donor. Patients with
disorders and diseases that damage the corneal epithelium, the outer surface of the
eye, and severely impair vision and the quality of life, such as those with ocular burns
and Steven-Johnson syndrome required this transplant but continued 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, persistent epithelial defects
and dry eye all can persist following a corneal transplant. The integrity of the corneal
epithelium relies upon the existence of limbal stem cells. According to Dua & AzuaraBlanco (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). Those 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 because of its unique
capabilities as a stem cell. The limbal cells will differentiate into corneal epithelial cells
after they are transplanted, improving visual acuity.
Scientists have begun exploring the potential of limbal stem cells in corneal
surface reconstruction. Use of autograft and allograft 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. Limbal cells are
taken from the healthy contralateral 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 and cyclosporine A the
most commonly used immunosuppressant. 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.