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This edition of the newsletter will summarize research on corneal development that was presented at the last ARVO meeting (Ft. Lauderdale, Florida, May, 1998). It will also present photos and information on some new instruments that have been developed for pediatric corneal transplant surgery in conjunction with Storz (Bausch & Lomb). At ARVO this year there was a symposium on Corneal Development and Maturation. It was moderated by Dr. James Zieske; featured speakers were Drs. D.C. Beebe, N.C. Joyce, 0. Sundin and H. Tseng. The Pax-6 gene (also known as the aniridia gene) found on chromosome 11 is the master control gene for eye formation (particularly of the anterior segment). It regulates many developmentally important genes through its action as a transcription factor. It is conserved through many species. In experimental animals a heterozygous anomaly in the Pax-6 gene can lead to aniridia, lens changes, corneal changes and retinal changes. During the course of embryologic development, the corneal epithelium differentiates from surface ectoderm at the same time as the lens epithelium develops. Subsequent to this there is an invasion of neural crest cells (secondary neural mesenchyme). These will form the corneal enclothelium, stroma, and keratocytes. The corneal extracellular matrix is then deposited and thus the early cornea is formed. Following these early developmental events the cornea continues to mature. As this process continues, endothelial cells stop proliferating and begin their pump function. The stroma begins to thin and dehydrate and the keratocytes become quiescent. The epithelial and endothelial tight junctions and hemidesmosomes form and eventually the conjunctiva and goblet cells appear. Coincidentally some of these events coincide with eyelid opening. Dr. Beebe's presentation postulates that the lens epithelium helps induce enclothelium formation and then controls and regulates enclothelial formation and formation of the anterior chamber. In the four day old chick the ectoderm has formed corneal epithelium and lens epithelium. By 7 days a corneal stroma, enclothelium and anterior chamber have developed. During this time there have been two waves of neural crest cells. In the first wave these mesenchymal cells have formed the enclothelium. The second wave forms the corneal stroma. The anterior chamber formed as the neural crest cells delaminate. Various experiments were performed on chick embryos between days 4 and 7 of development. If the lens epithelium was removed the enclothelium did not develop. If it was removed and then replaced corneal enclothelium and the anterior chamber formed. Therefore, in some way lens epithelium influences development of the corneal enclothelium and anterior chamber. The next paper by N.C. Joyce looks at enclothelial development in rats. Development ceases when membrane polarity occurred between the cells and when enclothelial cell division is inhibited by cell to cell contact. Once development ceases a mature Descemet's membrane develops. This all occurs between days 10 and 21 of embryologic development. Coincidentally these findings correlated with eyelid opening and expression of TGF beta, both of which occur between days 12, 13 and, 1A of development. Dr. Sundin presented additional data on the Pax-6 gene. The gene is involved with formation of the lens placode. From this placode the animal (chick) derives the lens epithelium and the ocular surface including corneal epithelium, conjunctiva and lacrimal glad (as it develops from the conjunctiva). No Pax-6 expression is found in the corneal stroma or endothelium. The gene is also required for maintenance of the ocular surface in adults. In mature mice Pax-6 is expressed in the corneal epithelium and conjunctiva. In these mice, heterozygous expression of Pax-6 leads to an influx of goblet cells into the corneal epithelium. This suggests that maintenance or proliferation of limbal stem cells is dependent on Pax-6 expression (and may explain the corneal, stem cell and lens changes seen in aniridia). For more information on this subject you can refer to the following:
DESIGNED FOR USE IN PEDIATRIC CORNEAL TRANSPLANTS
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