bromochloroacetic-acid and Pterygium

Pterygia are common ocular surface lesions thought to originate from limbal stem cells altered by chronic UV exposure. Traditionally regarded as a degenerative condition, pterygia also display tumor-like features, such as a propensity to invade normal tissue and high recurrence rates following resection, and may coexist with secondary premalignant lesions. This study was initiated to determine the rate of concurrent ocular surface diseases in patients with pterygia recruited from the practice of a single surgeon operating in a Sydney metropolitan hospital. One hundred pterygium specimens were histopathologically reviewed and selected cases were immunohistochemically assessed to confirm diagnosis. Along with previously documented typical features including epithelial proliferation, goblet cell hyperplasia, angiogenesis, inflammation, elastosis, stromal plaques, and Bowman's membrane dissolution, we identified five cases of ocular surface squamous neoplasia, six cases of primary acquired melanosis, two compound nevi (one suspect invasive melanoma), and one dermoid-like lesion. In 18 specimens, clusters of basal epithelial cells that coexpressed cytokeratin-15/-19 and p63-α were identified at the head of the pterygium, coinciding with clinical observation of Fuchs' flecks. Our data show that significant preneoplastic lesions may be associated with pterygium and that all excised pterygia should undergo histological examination. The presence of p63-α-positive epithelial cell clusters supports the hypothesis that pterygia develop from limbal epithelial progenitors.

Topics: Adult; Aged; Aged, 80 and over; Cell Aggregation; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nerve Growth Factors; Precancerous Conditions; Pterygium; Recurrence; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Stem Cells; Ultraviolet Rays; Young Adult

Pterygium is a vision-impairing fibrovascular lesion that grows across the corneal surface and is associated with sunlight exposure. To increase our understanding of the cells types involved in pterygium, we have used expressed sequence tag analysis to examine the transcriptional repertoire of isolated pterygium and to identify marker genes for tissue origin and cell migration.. An unnormalized unamplified cDNA library was prepared from 15 pooled specimens of surgically removed pterygia as part of the NEIBank project. Gene expression patterns were compared with existing data for human cornea, limbus, and conjunctiva, and expression of selected genes was verified by immunofluorescence localization in normal eye ocular surface and in pterygium.. Sequence analysis of 2,976 randomly selected clones produced over 1,800 unique clusters, potentially representing single genes. The most abundant complementary DNAs from pterygium include clusterin, keratins 13 (Krt13) and 4 (Krt4), S100A9/calgranulin B, and spermidine/spermine N1-acetyltransferase (SAT1). Markers for both conjunctiva (such as keratin 13/4 and AQP3) and corneal epithelium (such as keratin 12/3 and AQP5) were present. Immunofluorescence of Krt12 and 13 in the normal ocular surface showed specificity of Krt12 in cornea and Krt13 in conjunctival and limbal epithelia, with a fairly sharp boundary at the limbal-corneal border. In the pterygium there was a patchy distribution of both Krt12 and 13 up to a normal corneal epithelial region specific for Krt12. Immunoglobulins were also among the prominently expressed transcripts. Several of the genes expressed most abundantly in excised pterygium, particularly S100A9 and SAT1, have roles in cell migration. SAT1 exerts its effects through control of polyamine levels. IPENSpm, a polyamine analogue, showed a significant ability to reduce migration in primary cultures of pterygium. A number of genes highly expressed in cornea were not found in pterygium (several small leucine-rich proteoglycan family members) or were expressed at considerably lower levels (ALDH3A1 and decorin).. The expression pattern of keratins and other markers in pterygium most closely resemble those of conjunctival and limbal cells; some corneal markers are present, notably Krt12, but at lower levels than equivalent conjunctival markers. Our data are consistent with the model of pterygium developing from the migration of conjunctival- and limbal-like cells into corneal epithelium. Identification of genes with roles in cell migration suggests potential therapeutic targets. In particular, the ability of polyamine analogues to reduce migration in primary cultures of pterygium presents a possible approach to slowing pterygium growth.

Topics: Biomarkers; Cell Movement; Cells, Cultured; Clusterin; Conjunctiva; Cornea; Down-Regulation; Eye Proteins; Fluorescent Antibody Technique; Gene Expression Profiling; Gene Library; Gene Regulatory Networks; Humans; Keratins; Limbus Corneae; Polyamines; Pterygium; RNA, Messenger

This study was initiated after observation of some intriguing epithelial growth properties of contact lenses used as a bandage for patients after pterygium surgery.. To determine the efficacy of culturing human ocular surface epithelial cells on therapeutic contact lenses in autologous serum with a view of using this system to transfer epithelial cells to patients with persistent corneal or limbal defects.. Excess graft tissue resected from patients undergoing pterygium surgery (n = 3) consisting of limbal epithelium was placed on siloxane-hydrogel contact lenses (lotrafilcon A and balafilcon A). Limbal explants were cultured in media with 10% autologous serum. Morphology, proliferative capacity and cytokeratin profile were determined by phase contrast, light and electron microscopy, and immunohistochemical analysis.. Lotrafilcon A contact lenses sustained proliferation and migration from limbal tissue. Cells became confluent after 10-14 days and consisted of 2-3 layers with a corneal phenotype (CK3(+)/CK12(+)/CK19(-)) and a propensity to proliferate (p63(+)). Electron microscopy showed microvilli on the apical surface with adhesive projections, indicating that these cells were stable and likely to survive for a long term. Growth was not observed from limbal explants cultured on balafilcon A contact lenses.. A method for culturing human ocular surface epithelium on contact lenses that may facilitate expansion and transfer of autologous limbal epithelial cells while avoiding the risks associated with transplanting allogeneic tissue has been developed. This technique may be potentially useful for the treatment of patients with limbal stem cell deficiency.

Topics: Bandages; Cell Culture Techniques; Cell Proliferation; Cells, Cultured; Contact Lenses, Extended-Wear; Corneal Transplantation; Epithelium, Corneal; Humans; Hydrogels; Keratins; Limbus Corneae; Microscopy, Electron; Microscopy, Phase-Contrast; Pterygium; Silicones

To evaluate the expression patterns of several keratin proteins in pterygial epithelium.. The proteins of K8, K10, K14, K16 and AE3 in the epithelium of 8 pterygia and 4 normal conjunctiva were detected using immunofluorescent staining.. In pterygial epithelium, the staining patterns of 5 keratin proteins were different with normal conjunctiva. No staining of K8, K10 and K16 was detected in normal conjunctival epithelium, but in pterygial epithelium, K8 and K16 were present in full thickness and K10 was present in superficial cells. In normal conjunctiva, only base layer of epithelium showed positive staining with antibody of K14 and AE3 proteins, but they were present in the full thickness in pterygial epithelium and the antibody of AE3 protein stained the superficial cells heavily comparing with base cells.. The abnormal expression of keratin proteins (K8, K10, K14, K16 and AE3) in pterygia indicates that the epithelial cells in pterygia are in the state of hyperproliferation and keratinization, which may be the cause of the abnormal tear function in patients with pterygia.

Topics: Adult; Aged; Conjunctiva; Epithelium; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Middle Aged; Pterygium

The purpose of this study was to study the morphology and cytokeratin expression in the epithelia of pterygia. Impression cytology and immunohistochemical staining with antikeratin antibodies were performed in 32 eyes of 16 patients with pterygia. TUNEL stain and electron microscopy were also performed in surgical specimens ofpterygium. Squamous metaplasia-like epithelial cells were found in all specimens of impression cytology, especially in the head part. These specimens had positive immunostaining by antipancytokeratin antibodies, but not by anti-K12 AK2 mAb. Goblet cells were found around the area of these abnormal epithelial cells. TUNEL-positive cells were found in the epithelia of the pterygial head, but not in the body of pterygia and normal conjunctiva. The expressional patterns of keratin by these epithelial cells ofpterygia are consistent with the notion that they are derived from conjunctival epithelium and mimic the process of squamous metaplasia.

Topics: Aged; Aged, 80 and over; Epithelium; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; In Situ Nick-End Labeling; Keratins; Male; Metaplasia; Middle Aged; Pterygium

To report a case of conjunctival mucoepidermoid carcinoma occurring in a long-standing pterygium in a 33-year-old Cambodian man infected with the human immunodeficiency virus (HIV).. Review of clinical history and histopathologic findings.. A pterygium that was present for 8 years suddenly became highly inflamed and underwent rapid growth. After the initial diagnostic conjunctival and corneal biopsy showed mucoepidermoid carcinoma, subsequent additional deep excisions of the adjacent sclera and cornea were necessary to completely excise the tumor. Cytokeratin and mucicarmine stains were used to confirm the pathologic diagnosis of mucoepidermoid carcinoma.. Unique features of this case include the extremely young age of the patient (perhaps rendered susceptible by his HIV infection), the tumor masquerading as a pterygium, and the use of a hybrid lamellar and full-thickness corneoscleral resection requiring a complementary graft. Seventeen months after the resection, the patient is free of tumor; this was histopathologically confirmed with multiple random conjunctival biopsies.

Topics: Adult; Carcinoma, Mucoepidermoid; Carmine; Coloring Agents; Conjunctival Neoplasms; Diagnosis, Differential; HIV Infections; Humans; Keratins; Male; Pterygium