The goal of this study was to determine the cell origin of human pterygia. In order to determine the origin of these cells, longitudinal cryostat sections through five primary and two recurrent pterygia were studied immunohistochemically by finding limbal basal stem cell staining patterns as defined by monoclonal antibodies AE1 (staining positive) and AE5 (staining negative). In addition, sections were stained with antivimentin antibody. Altered limbal basal cells invading normal cornea along the basement membrane were identified in seven human pterygia with these specific monoclonal antibodies. A group of limbal basal cells (vimentin and AE1 positive) was always present between the dissolved edge of Bowman's layer and vascularized conjunctiva which contained goblet cells. Scattered patches of cells staining positive with both vimentin and AE5 (in addition to their AE1 staining) were also found in conjunctival epithelium growing on corneal basement membrane adjacent to the migrating limbal cells, indicating local infiltration by the altered limbal basal cells. This same pattern was also found in recurrent pterygia. Based on this data we propose that the pathogenesis of pterygia is due to a normal stationary parental limbal epithelial basal cell becoming altered and giving rise to a zone of motile daughter cells, the pterygium cells, which leave the limbal region and migrate as a group centripetally along the corneal basement membrane dissolving Bowman's layer. Since these altered limbal basal cells are found at the microscopic advancing edge over Bowman's layer with no fibroblast mass under them, the pterygium cell apparently precedes the rapid growth of the fibroblasts from the stroma.(ABSTRACT TRUNCATED AT 250 WORDS)

The finding of increased nuclear p53 in the limbal epithelium of pterygia, limbal tumors, and most pingueculae indicates the probable existence of p53 mutations in these cells as an early event in their development, which is consistent with their causation by UV radiation causation. In addition, due to a damaged p53-dependent programmed cell death mechanism, mutations in other genes are progressively acquired which allows the multi-step development of pterygia and limbal tumor cells from p53 positive cells overlying a Stage II pinguecula. Similarly, a pterygium dysplasia could arise from a pterygium cell. A classification for limbal basal cell tumors is proposed, and the different stromal changes in pingueculae, pterygia, and limbal tumors are identified. Two cell types were also identified: a p53-positive pinguecula limbal epithelial cell (a pinguecula II cell) and a p53-positive pterygium dysplasia cell (pterygium dysplasia cell).

Background: The tumor suppressor gene p53 is expressed without apoptosis in the limbal basal stem cells of all pterygia and limbal tumors and most pingueculae from which these growths seem to originate. Oncogenic human papillomaviruses (HPVs) have been found in pterygia and limbal tumors, and HPV and p53 overexpression commonly coexist in oropharyngeal and penile carcinomas. Objective: To search for HPV DNA as a cofactor in the development of pingueculae, pterygia, and limbal tumors. Methods: We examined specimens-1 of pinguecula, 13 of pterygia (7 primary, 1 recurrent, 1 with dysplasia, and 4 primary not tested for p53), and 10 of limbal tumors (2 with actinic keratosis dysplasia, 1 with conjunctival intraepithelial neoplasia, 3 with carcinoma in situ, and 4 with squamous cell carcinoma)-expressing p53. Specimens were tested for the presence of HPV DNA by the polymerase chain reaction using degenerate consensus primers for the highly conserved portion of the L1 region that encodes a capsid protein of the virus. This assay has a wide spectrum with capability of detecting essentially all known HPV types. Nested polymerase chain reaction was performed on all specimens. Primers of the CLINICAL SCIENCES

To assess the potential role of matrix metalloproteinases (MMPs) in the pathogenesis of pterygia by comparing the immunolocalization patterns of MMPs in altered limbal basal stem cells, activated fibroblasts, and areas of elastotic degeneration adjacent to the pterygia.Methods: Nine primary and 1 recurrent pterygia along with normal superior limbal-conjunctival tissue and cornea were immunostained with mouse monoclonal antibodies specific for MMP-1, MMP-2, MMP-3, MMP-9, membrane type 1 (MT1)-MMP (MMP-14), and membrane type 2-MMP (MMP-15).Results: Normal conjunctival, limbal, and corneal cells lacked significant immunostaining except for cell surface MT1-MMP. In contrast, altered limbal basal epithelial cells of the 9 primary and 1 recurrent pterygia immunostained for all 6 MMPs. Activated and altered fibroblasts associated with the pterygia immunostained primarily for MMP-1. In contrast, stromal areas of elastotic degeneration (pingueculae) showed variable immunostaining of MMPs.

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