bromochloroacetic-acid and Conjunctival-Diseases

The role of biomaterials in tissue engineering and regenerative medicine strategies to treat vision loss associated with damage to tissues in the anterior segment of the eye has been studied for several years. This has mostly involved replacement and support for the cornea and conjunctiva. These are complex tissues with specific functional requirements for different parts of the tissue. Amniotic membrane (AM) is used in clinical practice to transplant autologous or allogenic cells to the corneal surface. Fibrin gels have also progressed to clinical use under specific conditions. Alternatives to AM such as collagen gels, other natural materials, for example keratin and silks, and synthetic polymers have received considerable attention in laboratory and animal studies. This experience is building a body of evidence to demonstrate the potential of tissue engineering and regenerative medicine in corneal and conjunctival reconstruction and can also lead to other applications in the anterior segment of the eye, for example, the trabecular meshwork. There is a real clinical need for new procedures to overcome vision loss but there are also opportunities for developments in ocular applications to lead to biomaterials innovations for use in other clinical areas.

Topics: Amnion; Animals; Biocompatible Materials; Collagen; Conjunctival Diseases; Corneal Diseases; Humans; Keratins; Regenerative Medicine; Silk

To investigate the molecular mechanism of pathological keratinization in severe ocular surface diseases based on the process of epidermal physiological keratinization and the gene expression profile of ocular surface epithelium.. We examined conjunctiva covering corneas which had ocular surface diseases in which pathological keratinization was seen. We then investigated the expression of epidermal keratinization-related proteins and clusterin, which is the most abundant gene transcript in human corneal epithelium.. Semiquantitative reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry showed that transglutaminase 1, involucrin, filaggrin, and cytokeratin 1/10 expression was upregulated in keratinized conjunctiva compared to normal conjunctiva. On the other hand, the level of clusterin expression in the diseased ocular surfaces was significantly lower than normal. We also concluded that clusterin expression may depend on the severity of the pathological keratinization.. Various keratinization-related proteins and clusterin are most likely to be involved in the pathogenesis of cicatrizing ocular surface diseases.

Topics: Clusterin; Conjunctiva; Conjunctival Diseases; Filaggrin Proteins; Glycoproteins; Humans; Intermediate Filament Proteins; Keratinocytes; Keratins; Molecular Chaperones; Protein Precursors; Transglutaminases

Topics: Adolescent; Biomarkers; Choristoma; Conjunctival Diseases; Cysts; Female; Humans; Keratins; Respiratory Mucosa; Ultrasonography

To describe an acquired keratinizing cyst of the palpebral conjunctiva.. Observational case report with clinical and histopathologic correlations.. A 41-year-old man presented with diffuse mild left upper eyelid swelling, eye pain, and redness in the absence of a nodule. Eversion of the eyelid revealed a whitish-gray, well-demarcated, superficial 4 × 4 mm lesion on the medial portion of the palpebral surface accompanied by a large epithelial erosion in the superior aspect of the cornea. The lesion was excised completely, sparing the tarsus. The site of excision healed completely after 1 week with no recurrence during 6 months of follow-up. Histopathologically, the lesion consisted of a round, eosinophilic, compact, acellular mass of keratin. The cyst's epithelial covering was a mixture of mostly flattened but occasionally polygonal basaloid epithelial cells, sometimes with foci of parakeratosis and pigmentation. There was no apparent keratohyalin granular layer (trichilemmal rather than epidermoid keratinization).. The pathogenesis of this peculiar lesion is hypothesized to involve a pseudogland of Henle that developed trichilemmal keratinization. It represents another easily overlooked cause of corneal epithelial erosion.

Topics: Adult; Conjunctival Diseases; Cysts; Humans; Keratins; Male

To provide a new tool for the evaluation of altered ocular surfaces by using a combination of impression cytology, laser scanning confocal microscopy and advanced image analysis.. The expression of keratin 3 (K3), keratin 12 (K12), keratin 19 (K19) and mucin 1 (MUC1) was analysed by immunofluorescence on both histological sections of nine corneoscleral buttons from normal donors comprising conjunctiva, limbus and cornea and impression cytology specimens from six healthy normal subjects (12 eyes) and 12 patients with chronic ocular surface disorders. Levels of fluorescence expression of the different markers were quantified through quantitative fluorescence immunohistochemistry (Q-FIHC).. Impression cytology specimens from normal and diseased ocular surfaces showed distinct expression patterns for K12 and MUC1. Healthy corneas expressed only K12 (but not MUC1), while conjunctivalised corneas from patients with limbal stem cell deficiency (LSCD) were characterised by the presence of MUC1 and the disappearance of K12. Similar clear-cut results were not seen with the K3/K19 markers, which showed lack of specificity and overlapping signals in cornea and conjunctiva impression cytology specimens.. The ability of K12 and of the antibody against MUC1 to discriminate clearly between limbus/cornea and conjunctiva in impression cytology specimens could become a valuable diagnostic tool for ophthalmologists in order to evaluate alterations of the ocular surface and the grading of LSCD.

Topics: Adult; Aged; Biomarkers; Child, Preschool; Conjunctiva; Conjunctival Diseases; Cornea; Corneal Diseases; Cytodiagnosis; Diagnostic Techniques, Ophthalmological; Eye Proteins; Humans; Keratins; Limbus Corneae; Microscopy, Confocal; Middle Aged; Mucin-1

To clarify the relationship between clinical symptoms and histological status in patients with ocular cicatricial pemphigoid (OCP) and Stevens-Johnson syndrome (SJS).. Clinical symptoms of four OCP and eight SJS patients in the chronic phase were scored with our recently proposed grading system. The histological status of the pannus tissue removed from the corneal surface during surgery was investigated using immunohistological techniques.. All participants showed total loss of the palisades of Vogt and conjunctivalization of the entire corneal surface. All pannus tissues expressed the conjunctival epithelium marker CK4/13. The pannus tissue in clinically keratinized SJS expressed skin epidermal major cytokeratins, but the tissues of nonkeratinized SJS did not.. Clinical observation and the use of our recently proposed grading system agreed with the immunohistological status with respect to keratinization, cell proliferation, and corneal/conjunctival cell typing. These findings facilitate our understanding of the pathogenesis of OCP and SJS, and will hopefully contribute to the development of future treatment strategies and improve predictions of the postoperative prognosis of ocular surface reconstruction in patients with OCP and SJS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD; Biomarkers; Cell Proliferation; Chronic Disease; Conjunctiva; Conjunctival Diseases; Cornea; Corneal Diseases; Epithelial Cells; Female; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Pemphigoid, Benign Mucous Membrane; Preoperative Period; Stem Cells; Stevens-Johnson Syndrome; Visual Acuity; Young Adult

To evaluate the use of autologous serum (AS) from patients with severe ocular surface disease (OSD) in the development of transplantable corneal and oral epithelial tissue equivalents and to compare it with the use of conventional culture methods by using fetal bovine serum (FBS).. AS was obtained from patients with severe OSD secondary to Stevens-Johnson syndrome. Corneal and oral epithelial cells were cultivated in medium supplemented with either AS or FBS. Corneal and oral epithelial equivalents were constructed on denuded amniotic membranes. The bromodeoxyuridine (BrdU) ELISA cell proliferation assay and colony-forming efficiency (CFE) of cells cultivated in AS- or FBS-supplemented media were compared. The morphologic characteristics and the basement membrane assembly of cultivated epithelial equivalents were analyzed by light and electron microscopy, as well as by immunohistochemistry.. BrdU proliferation assay and CFE analysis showed that human corneal and oral epithelial cells cultivated in AS-supplemented media had comparable proliferative capacities compared with FBS-supplemented media. The corneal and oral epithelial equivalents cultivated in AS- and FBS-supplemented media were morphologically similar and demonstrated the normal expression of tissue-specific keratins and basement membrane assembly. The presence of a well-formed stratified epithelium, a basement membrane, and hemidesmosomal attachments was confirmed by electron microscopy.. AS-supplemented cultures were effective in supporting the proliferation of human corneal and oral epithelial cells, as well as the development of transplantable epithelial equivalents. The use of AS is of clinical importance in the development of autologous xenobiotic-free bioengineered ocular surface equivalents for clinical transplantation.

Topics: Adult; Aged; Basement Membrane; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cell Transplantation; Colony-Forming Units Assay; Conjunctival Diseases; Cornea; Culture Media; DNA; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Female; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Male; Microscopy, Electron, Scanning; Middle Aged; Mouth Mucosa; Serum; Stevens-Johnson Syndrome

To our knowledge there have been no studies on intermediate filament (IF) expression in conjunctival melanocytic tumors to date. Melanocytic lesions occurring at various body sites are known to express, in addition to the predominant IF protein vimentin, the epithelial-specific cytokeratins (CKs) and the neuronal IF peripherin. The present study was therefore carried out to assess the expression of IF proteins in conjunctival melanocytic lesions.. Paraffin-embedded material from 34 tumors - 16 conjunctival nevi, nine specimens of primary acquired melanosis (PAM; eight with and one without atypia), and nine conjunctival melanomas - was assessed after the application of a panel of antibodies directed against diverse IF proteins, including vimentin, CKs and peripherin.. The most significant finding of this study was that all the tumors investigated expressed vimentin exclusively. While simple-epithelium CKs were found in epithelial cysts of nevi and in pseudoglandular portions adjacent to the melanoma, they were not identified in the tumor cells themselves. Similarly, peripherin and neurofilaments were not detected within any of the tumor cells.. The IF expression pattern of conjunctival melanocytic lesions differs from that seen in melanocytic tumors of other body sites (including uveal melanomas), in that it includes neither CKs nor peripherin.

Topics: Conjunctiva; Conjunctival Diseases; Humans; Intermediate Filament Proteins; Keratins; Melanocytes; Membrane Glycoproteins; Nerve Tissue Proteins; Neurofilament Proteins; Peripherins; Vimentin

Topics: Conjunctiva; Conjunctival Diseases; Humans; Immunohistochemistry; Keratins; Membrane Proteins; Metaplasia; Mucous Membrane; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transglutaminases

In severe ocular surface diseases, pathologic keratinization of the ordinarily nonkeratinized corneal and conjunctival mucosal epithelia results in severe visual loss. The expression in conjunctivalized corneas of various proteins known to play important roles in the physiological keratinization process in human epidermis was examined to better understand the mechanism of keratinization.. Conjunctiva covering the cornea was examined in 12 eyes with ocular surface disease in the chronic cicatricial phase. These comprised four Stevens-Johnson syndrome, four ocular cicatricial pemphigoid, and four chemical injuries. Normal conjunctivas from four age-matched individuals served as controls. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to investigate transglutaminase 1 gene expression and immunohistochemistry to study the expression of transglutaminase 1 protein along with other keratinization-related proteins (involucrin, loricrin, filaggrin, and cytokeratins 1 and 10) and cytokeratin pairs 4/13 and 3/12.. Semiquantitative RT-PCR showed that transglutaminase 1 mRNA expression was upregulated in keratinized conjunctiva compared with normal. Also, in this tissue, immunohistochemistry demonstrated elevated levels of transglutaminase 1, involucrin, filaggrin, and the cytokeratin pair 1/10. Levels of loricrin and cytokeratin pairs 4/13 and 3/12, however, remained the same.. Various keratinization-related proteins, transglutaminase 1 included, are most likely involved in the pathogenesis of cicatrizing ocular surface diseases.

Topics: Adult; Aged; Aged, 80 and over; Conjunctiva; Conjunctival Diseases; Female; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Humans; Intermediate Filament Proteins; Keratins; Male; Membrane Proteins; Middle Aged; Pemphigoid, Benign Mucous Membrane; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stevens-Johnson Syndrome; Transglutaminases; Up-Regulation

Keratinization of the ocular surface epithelium is associated with various disorders impairing vision. We immunohistochemically determined whether the ocular surface epithelia express involucrin, and whether its expression pattern may differ in benign vs. malignant disorders. Expression of cytokeratins was also examined to provide further information relative to the epithelial differentiation.. We evaluated 17 specimens; 6 specimens of the normal ocular surface epithelia, 3 specimens from cases of conjunctival intraepithelial neoplasia (CIN), 6 of conjunctival squamous cell carcinoma (SCC) and 2 of conjunctivae from cases of superior limbic keratoconjunctivitis (SLK).. Corneal epithelium exhibited intracellular immunoreactivity for involucrin. Four of the 6 specimens of bulbar conjunctival epithelium showed involucrin immunoreactivity in the perimembranous region, whereas the fornical conjunctiva was negative. Cornified envelope in SLK specimens was positive for involucrin. The CIN showed its immunoreactivity in the perimembranous region in all levels of the hyperproliferative epithelium without keratinization, i.e., similar to the bulbar conjunctiva. The neoplastic cells of well-differentiated SCC showed involucrin in the perimembranous region, and those of moderately- to poorly-differentiated SCC have involucrin in their cytoplasm. The expression pattern of cytokeratins was unrelated to grade of malignancy in ocular SCC.. The epithelia of normal subjects and of CIN expresses involucrin without keratinization. In contrary, the keratinized SLK epithelium markedly expresses involucrin in the cornified envelope. The subcellular immunolocalization of involucrin in the ocular SCC may help in evaluating the differentiation, i.e., malignancy, of neoplastic cells.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Conjunctiva; Conjunctival Diseases; Conjunctival Neoplasms; Epithelium; Eye Proteins; Female; Filaggrin Proteins; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Keratoconjunctivitis; Male; Middle Aged; Protein Precursors

Seborrheic keratosis on the conjunctiva appears to have never been reported in the literature. The authors report here a well-documented case of seborrheic keratosis of conjunctiva clinically simulating a malignant melanoma.. Case report.. A 66-year-old man presented with a juxtalimbal pigmented tumor involving the temporal conjunctiva of his left eye. Because of the rapid enlargement of the mass within a period of 5 months, a clinical diagnosis of malignant melanoma was made. Cytopathologic examinations were performed by impression cytology before the patient underwent a wide en-block excision of the tumor.. Cytologic features were studied by impression cytology with periodic acid-Schiff-Papanicolaou stain. Immunochemical characteristics of tumor cells were studied by immunochemical stain of cytokeratin and HMB-45. Tumor morphology was observed by histopathologic examination.. Impression cytology disclosed basaloid cells intermixing with squamoid cells, and these cells demonstrated positive immunoreactivity to cytokeratin and no reactivity to HMB-45. Histopathologic examination of the tumor specimen established the diagnosis of seborrheic keratosis, and the results of immunohistochemical staining were consistent with those of the impression cytology with immunocytochemical staining.. The authors describe the first case report of conjunctival seborrheic keratosis and present its immunocytochemical and immunohistochemical characteristics. Such a benign lesion can clinically mimic a malignant melanoma.

Topics: Aged; Antigens, Neoplasm; Conjunctival Diseases; Conjunctival Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Keratosis, Seborrheic; Male; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins

Topics: Aged; Anterior Chamber; Cataract Extraction; Conjunctival Diseases; Cysts; Epithelium; Humans; Keratins; Male; Postoperative Complications; Suppuration

To elucidate the pathophysiologic features of conjunctival concretions, we performed polarized microscopic examinations, immunocytochemical studies, histochemical stains, and electron microscopic studies of concretions obtained from five patients with chronic conjunctivitis. Electron-dense secretory granules, ranging from 0.2 to 0.5 micron in diameter and stained positively for periodic acid-Schiff and mucicarmine, were found in the superficial lining epithelial cells of the pseudogland of Henle. In view of the granular and membranous figures reflecting degenerating epithelial cells and secretory granules in the concretions, we argue that the concretions, are mostly composed of the mucinous secretion of the transformed conjunctival glands admixed with the degenerative products of the epithelial cells.

Topics: Adolescent; Adult; Calculi; Conjunctiva; Conjunctival Diseases; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Polarization

Conjunctival leucoplakia was induced by the local beta-blocker metipranolol in one case. Withdrawal of the drug and application of all-trans retinoic acid ointment resulted in resolving of the keratinisation. A striking pharmacological resemblance is discovered between metipranolol and practolol. Metipranolol seems to be a less toxic phenol derivative of practolol. Nevertheless, it seems able to act as antigen.

Topics: Chemical Phenomena; Chemistry; Conjunctival Diseases; Epinephrine; Female; Humans; Keratins; Metipranolol; Middle Aged; Propanolamines

We report four cases of corneoconjunctival keratinization that were successfully treated with topical retinoic acid ointment. In two cases keratinization was due to squamous metaplasia and in two others it was secondary to intraepithelial corneoconjunctival neoplasia. Treatment reversed severe keratinization in a case of drug-induced pseudopemphigoid and stabilized the disease in one of the two affected eyes without additional treatment. In a case of ocular cicatricial pemphigoid, retinoic acid was useful as an adjuvant therapy to immunosuppression, by reversing keratinization of the conjunctiva. In two cases of corneoconjunctival neoplasia, lesions regressed markedly. Long-term treatment was well tolerated in three patients. Our findings suggest that retinoic acid ointment is effective in treating severe squamous metaplasia in cicatrizing diseases of the conjunctiva. Our findings indicate further that retinoic acid seems to inhibit growth of corneoconjunctival neoplasias and thus might be useful complementary therapy in this situation.

Topics: Administration, Topical; Aged; Aged, 80 and over; Conjunctiva; Conjunctival Diseases; Conjunctival Neoplasms; Conjunctivitis; Cornea; Corneal Diseases; Epithelium; Female; Humans; Keratins; Male; Metaplasia; Tretinoin

Sixty consecutive cases of dermis-fat grafts for anophthalmic socket reconstruction were reviewed to examine the frequency, severity, and management of postoperative complications. In seven patients, the conjunctiva failed to resurface the graft and central ulceration developed. Ten cases resulted in enophthalmos. Two patients developed keratinized sockets with chronic discharge and desquamation. Three patients required excision of conjunctival granulomas. One patient developed a primary graft infection. A donor site hematoma occurred in one patient. Secondary surgical intervention was required in ten patients. Nine complications in eight patients were managed in the office; five complications in four patients were observed and subsequently resolved without surgical intervention. Most complications occurred in patients with severely traumatized sockets who had undergone extensive earlier ocular surgery, or who had a systemic disease contributing to defective wound healing.

Topics: Adipose Tissue; Adult; Aged; Anophthalmos; Child; Conjunctiva; Conjunctival Diseases; Eye Diseases; Granuloma; Hematoma; Humans; Infant; Keratins; Middle Aged; Postoperative Complications; Skin Transplantation; Surgery, Plastic; Surgical Wound Infection; Ulcer