What a Study of Pterygia Teaches us About the Cornea? Molecular Mechanisms of Formation

Experiments were carried out in the early 1990s to investigate the cell types involved in a pterygium and to determine a possible mechanism of formation. Our first experiments used monoclonal antibodies to keratins and an associated protein (vimentin), to look at the cells that compose a pterygium. These experiments demonstrated that a pterygium is the result of an abnormal limbal basal epithelial stem cell that moves onto Bowman's layer and brings about the dissolution of this layer. More importantly, these data showed that the clear corneal epithelial cells in front of the pterygium also contained these abnormal limbal cells, which we named the pterygium cell. This demonstrated that when a pterygium is removed, a wide area of what appears to be normal epithelium must be removed to inhibit reoccurrence of the growth. Later experiments using expressed sequence tag analysis of an un-normalized unamplified complementary DNA library from surgically removed pterygia were compared with normal cornea and confirmed the role of the epithelial cells in this growth. The gene expression studies also showed that genes involved in cellular migration are stimulated, and this led to studies on polyamine analogs as inhibitors of pterygial migration. Immunohistochemical studies with antibodies to matrix metalloproteinases (MMPs) showed that it is the pterygium cell that produces the MMPs that dissolve Bowman's layer resulting in the growth stimulation of stromal fibroblasts. This led to experiments on the use of MMP inhibitors to inhibit the growth of pterygia.