Limbal stem cells

Tseng SCG. Concept and application of limbal stem cells. Eye 3 141-157 (1989). 

It has been well known for a long time that the renewal of the comeal epithelium depends on the lim-bal stem cells. At first considered as a simple theory [7], supported by several publications [8, 14], the lim-bal stem cells are now coimnonly used in transplantation as a treatment to numerous pathologies including bums. This transplantation of limbal stem cells is one of the rare successful cases of therapeutic use of stem cells for human patients [7]. 

The construction of the eye is completely different. The outer layer of this mucosa consists of a tiny tear layer of lipids and water which covers a superficial epithelium closed by double layer lipid membranes of 30-70 nm size interconnected by tight jnnctions. Three to seven layers of epithelial cells cover the stromal structures of conjunctiva or cornea. The conjnnctival surface has interposed cells secreting small amonnts of mucin, the so-called goblet cells, which are typically missing within the corneal epithelinm. The regeneration of epithelial structnres is dne to the limbal stem cells located deep in the Vogt s crypts, for the cornea. 

The limbus is the anatomic junction between the transparent cornea and the conjunctiva, a tissue in which the vessels circulate. At this level, there would be the limbal stem cells, cells generating the differentiated epithelial cells of the cornea. The essential property of the cornea is transparency. The seriousness of the ocular bum consists in the loss of the comeal transparency. Actually the limbus is a real barrier to the conjunctiva. In the following months, a serious ocular bum will result in the development of a conjunctival cover leading to a loss of vision. 

Conjunctival ischemia is the major sign of chemical bums the extent of this ischemia is the medium of evaluation of the secondary ability of back growth of the comeal epithelium. Even before the theory of corneal limbal stem cells was mentioned, Hugues had... 

A complete comeal ulcer is a sign of the seriousness of a bum. The theory of the limbal stem cells may explain that experimental fact. Actually, in that theory, those cells, which are the only ones to regenerate some mature epithelial comeal cells, would be located around the comeal epithelium. Like the conjunctival ischemia, the complete comeal ulcer is an indirect sign of probable destmction of the limbal stem cells. Nevertheless, a complete comeal ulcer or a comeal ulcer that completely releases the optical axis, does not cause any loses of visual acuity. 

The spontaneous evolution of this type of ulcer is dramatic and within a few weeks results in the conjunctival covering. This phenomena begins in the zone where limbal stem cells are the most insufficient, that is, as a general rule, in the inferior part. It gradually develops over the entire corneal surface and Anally results in a complete conjunctiva that is completely covered and a loss of visual function of the damaged eye (Figs. 7.13 and 7.14). 

Sometimes, the presence of a noisy symptomatology can make the initial clinical examination difficult, although the latter enables to draw up a prognosis and mostly to drive the surgical care. The condition of the cornea is the major element in the definition of the surgical behavior. It is crucial to know whether there is or is not destruction of the limbal stem cells. 

Stoiber, J., Muss, W.H., Pohla-Gubo, G., Ruckhofer, J., Grabner, G. Histopathology of human corneas after amniotic membrane and limbal stem cell transplantation for severe chemical burn. Cornea 21, 482-489 (2002)... 

Gomes, J.A., Dos Santos, M.S., Cunha, M.C., Mascaro, V.L., Barros, J.N., De Sousa, L.B. Amniotic membrane transplantation for partial and total limbal stem cell deficiency secondary to chemical bum. Ophthalmology 110, 466-473 (2003)... 

Fogla, R., Padmanabhan, R Deep anterior lamellar keratoplasty combined with autologous limbal stem cell transplantation in unilateral severe chemical injury. Cornea 24, 421-425 (2005)... 

More severe burns typically require extensive medical and surgical treatment. Ascorbate and citrate have been shown to reduce the risk of corneal ulceration and perforation.The use of topical sodium citrate 10% and topical sodium ascorbate 10% every 2 hours and oral vitamin C (500 mg) every 6 hours has been recommended fc>r grades n, HI, and IV burns. Oral tetracyclines have also been shown to reduce collagenase activity, decreasing corneal ulceration after chemical burns. Doxycycline 100 mg twice daily is recommended for grades n, HI, and IV chemical burns. Surgical options include conjimctival transplantation, amniotic membrane transplantation, limbal stem cell transplantation, and lamellar keratoplasty. 

A successful clinical study was conducted by using limbal-derived cell sheets for the treatment of patients suffering from unilateral total corneal stem-cell deficiencies [18], which resulted from alkali burns or Stevens-Johnson syndrome. In the case of bilateral total comeal stem-cell deficiencies, an autologous oral mucosal epithelial cell sheet was transplanted onto the ocular surface [19]. A clinical trial in France for the treatment of a bilateral limbal stem-cell deficiency had been conducted by using autologous oral mucosal epithelial cell sheets [20]. Through this clinical trial, the treatment was safe and effective in 25 cases with a 1-year follow-up, although two patients experienced serious adverse events, which were not related to the transplantation of the cell sheets. 

D. Amniotic membrane transplantation with or without lim-bal allografts for comeal surface reconstmction in patients with limbal stem cell deficiency. Arch Ophthalmol 116(4), 431-441 (1998)... 

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