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 like…be specific. In the past, such disorders were a problem for surgeons and patients and posed a challenge to treat completely.-why? What is the problem? Avoid being vague. If you are going to say they are challenging to treat then say why. 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.-split up this sentence. Patients with diseases that damage the corneal epithelium, the outer surface of the eye-what’s the difference between the cornea and corneal epithelium?, have impaired vision and compromise the quality of their life.-You are jumping all over the place. First you talk about the struggles in the beginning, then the treatment and now you are back to the struggles… Organize this. Those with ocular disorders such as burns and Steven-Johnson syndrome-say what? Do you think the general audience has any idea what this syndrome is? 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-how often? fail to improve vision (Burman & Sangwan, 2008). Ocular surface scarring; the formation of vessels and capillaries; persistent epithelial defects and dry eye can persist following a transplant.do all these impair vision? 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-what?, simultaneously replicating and producing cells with high fidelity; potency; differentiation into different cell lineages; and slow cell cycling.you are forgetting your audience…simplify the language. 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).-who is pelligrini and why didn’t this person write the paper? Limbal stem cell transplants have yielded promising results and are now used to treat ocular surface disorders by the medical community. You need to clean up this intro. Organize your thoughts. Use your outline. You might want to start with stem cells and then go into on of there uses as a treatment for the diseases you are discussing. Simplify the language also. Limbal stem cells are supported by a unique microenvironment called the stem cell niche.-I am going to stop reading here. You need to bring this down to Earth. 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. The number below will change with each revision. These numbers are simply indicative of the amount of improvement required at this point. When you receive a 9 or greater, the review is ready. DrT 6/10