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S Saika

Publications and source records attributed to S Saika.

At least 37 records · Page 2Linked to original sources

Immunolocalization of TGF-beta1, -beta2, and -beta3, and TGF-beta receptors in human lens capsules with lens implants.

PURPOSE: To establish the alteration in expression pattern of transforming growth factor (TGF)-betas and their receptors during repair of lens capsules after cataract surgery, we immunohistochemically located TGF-beta isoforms and their receptors in human lens capsules before and after cataract surgery. METHODS: Ten post-cataract surgery capsular specimens were obtained during vitrectomy. Three sections of the anterior capsules were obtained during cataract surgery. A whole lens capsular bag immediately after lens extraction was obtained during vitrectomy. Cryosections of these specimens were processed for immunohistochemical analysis for TGF-beta1, TGF-beta2, TGF-beta3, TGF-beta receptor type I (TbetaR-I), type II (TbetaR-II) and type III (TbetaR-III), and were observed under light micros-copy. RESULTS: Lens epithelial cells (LECs) lining the inner surface of the anterior capsules exhibited immunoreactivity for TGF-beta2 and TbetaR-II. Immunoreactivity for TGF-beta1, -beta3, TbetaR-I and TbetaR-III was negative. In the whole capsular bag specimen, equatorial LECs were positive for TGF-beta1 and -beta2, but not for -beta3. In post-cataract surgery specimens, antibodies for each TGF-beta isoform labelled either the LECs or ECM accumulated on the capsules. Post-surgical LECs expressed TbetaR-I and TbetaR-II, and had also TbetaR-III in seven of the nine specimens examined. CONCLUSION: Expression pattern of TGF-beta s in quiescent LECs showed regional heterogeneity. Anterior LECs exhibited TGF-beta2 immunoreactivity, while equatorial LECs were positive for TGF-beta1 and -beta2. Quiescent LECs expressed TbetaR-II. LECs proliferating around IOLs expressed proteins of each TGF-beta isoform and each TbetaR. TGF-beta s were also localized in the ECM on capsules undergoing repair. TGF-beta3, TbetaR-I and TbetaR-III are up-regulated in LECs after cataract surgery.

Adult↗

Transforming growth factor-beta isoform proteins in cell and matrix deposits on intraocular lenses.

PURPOSE: To determine whether the cells that adhere to poly(methyl methacrylate) (PMMA) posterior chamber intraocular lenses (PC IOLs) implanted in human eyes produce transforming growth factor-beta (TGF-beta) isoforms and whether the acellular proteinaceous deposits on these IOLs contain TGF-beta. SETTING: Department of Ophthalmology, Wakayama Medical College, Japan. METHODS: Thirty-two PMMA PC IOLs explanted from Japanese patients were immunostained for TGF-beta1, -beta2, or -beta3, and observed under light microscopy. RESULTS: Cell deposits were observed on 12 IOLs and proteinaceous deposits on 16. Components of the cell deposits were mainly of macrophage origin. The cell and matrix deposits tested positive for each isoform of TGF-beta. CONCLUSION: The cells that adhered to implanted PMMA PC IOLs produced TGF-beta, and the extracellular matrix that accumulated on the surface of the IOLs contained TGF-beta. Transforming growth factor-beta from the cells on IOLs may influence the healing process of residual lens capsules after cataract surgery with IOL implantation.

Adult↗

Expression of involucrin by ocular surface epithelia of patients with benign and malignant disorders.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Adult↗

Matrix metalloproteinases and tissue inhibitors of metalloproteinases of fibrous humans lens capsules with intraocular lenses.

PURPOSE: We located immunohistochemically the matrix metalloproteinases (MMP) -1, -2, -3 and -9 and the tissue inhibitors of matrix metalloproteinases (TIMP) -1 and -2 in the fibrous capsule of patients with intraocular lenses (IOLs). METHODS: During vitreoretinal surgery in 10 patients we obtained post-cataract surgery lens capsules with or without an IOL. The mean interval between the previous cataract operation and the extraction of the specimens was 35.2 months (range: 2-120 months). Circular sections of the anterior capsule with lens epithelial cells (LECs) were also obtained during cataract surgery. Specimens were processed for immunohistochemical identification of MMPs and TIMPs by light microscopy. RESULTS: While all the members of MMPs and TIMPs were not detected in the normal anterior capsules, they were detected in the ECM and/or LECs on the lens capsules extracted within 18 months after IOL implantations in all of the 4 patients, but were not observed in specimens obtained 18 months or longer postoperatively. In LECs of 1 capsule specimen 10 years postoperatively, MMP-1, but not other MMPs and TIMPs, was detected. CONCLUSIONS: MMPs and TIMPs were detected in the ECM and/or LECs on post-cataract surgery capsules. These proteins may be remodeling the newly deposited ECM and regulating LEC behavior on residual lens capsules in the early phase of healing after cataract surgery.

Adult↗

Silicone and poly(methyl methacrylate) lens decentration associated with asymmetric capsule shrinkage in rabbits.

PURPOSE: To determine whether silicone intraocular lenses (IOLs) are readily affected by capsule shrinkage. SETTING: Department of Ophthalmology, Wakayama Medical College, Wakayama, Japan. METHODS: A D-shaped incision was made in the anterior capsule of 38 eyes of 20 white rabbits. One of 2 IOL types was implanted in the capsular bag: 3-piece silicone or single-piece all-poly(methyl methacrylate) (PMMA). Twenty-eight eyes were evaluated for IOL rotation and optic decentration. RESULTS: The extent of postoperative decentration and rotation observed with the silicone IOLs did not significantly exceed that of the PMMA IOLs. CONCLUSIONS: Our results, coupled with the advantages of small incision surgery, indicate that a silicone IOL is an effective choice.

Animals↗

Immunolocalization of transcription factor AP1 in human ocular surface epithelia.

PURPOSE: The present study examined whether normal human ocular surfcae epithelia express AP1 components. Changes in expression patterns of these components in a case of ocular surface epithelial dysplasia was also evaluated before and after topical mitomycin C treatment. METHODS: Specimens of normal corneas (n = 2) and conjunctiva (n = 4) were obtained from 4 patients during cataract surgery or post mortem, while specimens of dysplastic epithelial tissue from the limbus were obtained from one patient. Specimens were immunohistochemically studied using antibodies against components of AP1. RESULTS: The normal corneal epithelium showed no staining with antibodies against c-Fos, Fra-2, FosB, c-Jun or JunB, whereas the limbal and bulbar conjunctival epithelia were positive for c-Fos, Fra-2, and c-Jun. Anti-FosB and -JunB antibodies reacted weakly with the conjunctival epithelium. JunD was absent in normal corneal and conjunctival epithelia. The dsyplastic epithelium showed positive labelling for c-Fos, Fra-2, c-Jun, and JunD throughout its thickness. Fra-1 was present in all specimens of epithelia examined. The dysplastic epithelium treated with mitomycin C was not labeled by anti-c-Fos or -Fra-2 antibody. CONCLUSION: Individual AP1 components show specific expression patterns in normal ocular surface epithelia and a case of dysplastic epithelium before and after topical MMC treatment, implying that these factors may play important roles in modulating epithelial cell function, e.g., proliferation and differentiation.

Adult↗

Immunohistochemical and ultrastructural analysis of dysplastic epithelium of human ocular surface: basement membrane and intermediate filament.

PURPOSE: The dysplastic corneal epithelium is characterized by the abnormal proliferation of epithelial cells. The phenotypes of these cells have not been elucidated. We investigated whether such epithelium expresses the phenotypes of corneal or conjunctival epithelial cells. METHODS: The corneas and conjunctivae from four normal subjects and from one patient with epithelial dysplasia of the central cornea were immunostained for IV and VII collagens and for cytokeratins. Monoclonal antibodies against collagen IV reacted to the [alpha1(IV)]2alpha2(IV) or alpha5(IV) molecule. Anti-cytokeratin antibodies were used to define epithelial cell types. The ultrastructure of the basement membrane (BM) of each specimen also was examined. RESULTS: Type VII collagen immunoreactivity was detected in all the specimens of epithelial BM. The anti-collagen IV [alpha1(IV)]2alpha2(IV) antibody labeled the conjunctival BMs, not the BMs of the corneal epithelia, of each subject. The normal corneal epithelial BM, not the BM of the conjunctival or dysplastic corneal epithelium, was immunolabeled with anti-alpha5(IV) antibody. The pattern of cytokeratin expression in the corneal epithelial dysplasia resembled that seen in the normal conjunctivae. Small breaks in the BM of dysplastic corneal epithelium were ultrastructurally revealed. The number of hemidesmosomes in the dysplastic corneal epithelium was decreased as compared with that in the normal BM. CONCLUSION: The composition of collagen types within the BM and the cellular phenotype of the dysplastic epithelium in the cornea resembled those of conjunctival epithelium, not of the cornea.

Adult↗

Immunolocalization of prolyl 4-hydroxylase subunits, alpha-smooth muscle actin, and extracellular matrix components in human lens capsules with lens implants.

Lens capsules become fibrotic after the extraction of a cataract. To understand this phenomenon, we evaluated the immunolocalization of prolyl 4-hydroxylase (an enzyme involved in procollagen hydroxylation), and extracellular matrix components and cytoskeletal components in a normal human lens capsule and in others with intraocular lenses. Lens capsules containing intraocular lenses were removed from a patient with proliferative vitreoretinopathy and three with proliferative diabetic retinopathy during vitreous surgery. Two circular sections of the anterior capsules with lens epithelial cells were obtained by anterior capsulotomy during cataract surgery. In addition, a lens capsular bag was obtained immediately after phacoemulsification. The lens capsules were processed for light microscopic immunohistochemical detection of the alpha and beta subunits of prolyl 4-hydroxylase, extracellular matrix components (including collagen types, laminin and cellular fibronectin) or cytoskeletal components (such as cytokeratin, vimentin and alpha-smooth muscle actin). Monolayer lens epithelial cells were seen on the inner surface of the normal anterior capsules. Each intraocular lens was found to be fixed in the capsular bag. Light microscopic immunohistochemistry showed that these proliferating cells expressed vimentin and alpha-smooth muscle actin; in contrast, quiescent lens epithelial cells did not stain for alpha-smooth muscle actin. Marked immunostaining for subunits of prolyl 4-hydroxylase was detected in lens epithelial cells proliferating on the capsules, while no or only faint prolyl 4-hydroxylase immunoreactivity was detected in quiescent lens epithelial cells immediately after phacoemulsification. Collagen types I, III and VI and cellular fibronectin were observed diffusely in accumulated connective tissue on a capsule with an intraocular lens. Type IV collagen immunoreactivity was seen both in the capsules and in the connective tissue accumulation on the capsules. Collagen V and laminin were detected in association with cellular proliferation. Collagen VII and VIII and laminin 5 were not seen. We concluded that during wound healing of the lens capsule after cataract extraction, the lens epithelial cells that proliferate on the inner surface of the capsule transform it into a myofibroblastic phenotype, expressing prolyl 4-hydroxylase and alpha-smooth muscle actin. These proliferating cells are involved in the production of collagen on the lens capsule. This results in a postoperative fibrotic process and contraction of the lens capsule.

Actins↗

Subretinal administration of tissue-type plasminogen activator to speed the drainage of subretinal hemorrhage.

BACKGROUND: Bleeding into the subretinal space in the vicinity of the macula is associated with age-related macular degeneration or retinal arterial macroaneurysm. The prognosis for restoration of vision is poor in the presence of blood clots. METHODS: Using a simple device composed of three disposable syringes we injected tissue-type plasminogen activator (tPA) into the subretinal space during conventional vitrectomy in six patients to assist the draining of subretinal clots. RESULTS: Four of six patients recovered their visual acuity postoperatively, while visual acuity in the other patients was stabilized. CONCLUSION: Early drainage of subretinal hemorrhage assisted by the introduction of tPA into the subretinal space led to uncomplicated surgery and favorable postoperative results.

Aged↗

Immunohistochemical evaluation of cellular deposits on posterior chamber intraocular lenses.

PURPOSE: We used immunohistochemistry to characterize cellular and proteinaceous deposits on the surfaces of explanted posterior chamber intraocular lenses (PC-IOLs). METHODS: A total of 30 PC-IOLs were immunostained for the alpha- or beta-subunits of prolyl 4-hydroxylase, which is involved in collagen biosynthesis; cellular fibronectin; alpha B crystalline; and CD68, a macrophage marker, to characterize the cellular deposits that adhere to the IOL surfaces and to evaluate the distribution of cells involved in the deposition of extracellular matrix on IOLs. RESULTS: Cellular or proteinaceous deposits were observed on all 30 PC-IOLs. Cells that showed positive staining for alpha B crystallin were classified as lens epithelial cells; CD68-positive cells were considered to be of macrophagic origin. Positivity for cellular fibronectin, including the macrophages and related cells, appeared to be responsible for the accumulation of fibronectin on the surfaces of PC-IOLs. Prolyl 4-hydroxylase-positive cells were involved in the deposition of collagen on PC-IOLs. CONCLUSION: Immunohistochemical study revealed that macrophages, foreign-body giant cells, and lens epithelial cells adhered to explanted PC-IOLs. Such adherent cells are responsible for the deposition of extracellular matrix on the surfaces of PC-IOLs and may regulate the assembly of the extracellular matrix, influencing the biocompatibility of PC-IOLs.

Adult↗

Immunolocalization of proto-oncogene products in keratocytes after epithelial ablation, alkali burn and penetrating injury of the cornea in rats.

BACKGROUND: We examined the immunolocalization of proto-oncogene products, including c-Fos and c-Jun, in the rat cornea during epithelial and stromal wound healing after simple epithelial ablation, penetrating injury or alkali burn. METHODS: Eighty-four male Wistar rats were divided into three groups and subjected to treatments as follows: (a) ablation of central corneal epithelium leaving basement membrane intact, (b) alkali burn in the central cornea with 1 N NaOH and (c) penetrating injury at the central cornea. The affected eyes were then enucleated after various intervals of healing. The frozen sections were immunohistochemically stained with the antibodies against proto-oncogene products. RESULTS: c-Fos- and c-Jun-immunoreactive cells were detected in the epithelium around the epithelial defect from 60 to 120 min after these treatments. The distribution of these cells were varied in these three types of injury. The immunoreactivities for these proteins were also detected in keratocytes after epithelial ablation. In the corneas with alkali burn, the immunoreactivities were detected in the keratocytes in the whole corneal stroma, and these immunoreactions were stronger than those observed in simple epithelial ablation. In the corneas with penetrating injury, such immunoreaction was seen only in keratocytes around the wound. CONCLUSION: These findings indicate that activator protein 1-mediated transcriptional activation for epithelial migration is initiated in the early phase after each injury, and that stromal keratocytes are also transcriptionally activated not only by alkali burn or penetrating injury but also by simple epithelial ablation in which basement membrane was not affected.

Animals↗

Immunolocalization of prolyl 4-hydroxylase in rabbit lens epithelial cells.

PURPOSE: To localize the enzyme prolyl 4-hydroxylase in the crystalline lens and determine the ability of lens epithelial cells (LECs) to synthesize procollagen. SETTING: Research laboratory, Department of Ophthalmology, Wakayama Medical College, Wakayama, Japan. METHODS: Phacoemulsification and aspiration of the crystalline lens followed by implantation of a poly(methyl methacrylate) intraocular lens (IOL) were performed in 1 eye each of 6 albino rabbits; the eye was enucleated 1 or 2 months later. Crystalline lenses were also extracted from the eyes of 2 rabbits. These samples were processed for immunohistochemical detection of the alpha- and beta-subunits of prolyl 4-hydroxylase. RESULTS: A monolayer of LECs was detected on the inner surface of the intact anterior capsule. Antibodies directed against both subunits of prolyl 4-hydroxylase reacted strongly to LECs proliferating on capsules with IOLs, whereas little or no reaction was observed in quiescent LECs or in the regenerated lenticular structure. CONCLUSION: The presence of prolyl 4-hydroxylase in LECs proliferating on the inner surface of the lens capsule suggests that these cells are involved in the production of procollagen and fibrosis during capsular injury and repair. Suppression of prolyl 4-hydroxylase activity may prevent the capsule opacification that results from cataract removal and IOL implantation.

Animals↗

Immunolocalization of hyaluronan and CD44 in quiescent and proliferating human lens epithelial cells.

PURPOSE: To investigate the role of hyaluronan and its receptor CD44 in capsular repair, their localization in opacified human posterior capsules and in lens epithelial cells (LECs) was assayed. SETTING: Research laboratory, Department of Ophthalmology, Wakayama Medical College, Japan. METHODS: In 8 patients, circular sections of the anterior capsules obtained during cataract surgery, the extracted crystalline lens, and the opacified lens capsules resulting from intraocular lens implantation were examined immunohistochemically to detect hyaluronan or CD44. RESULTS: Both hyaluronan and CD44 were found in the extracellular matrix that accumulated on the inner surface of the capsular bags. In contrast, LECs exhibited immunoreactivity to CD44 but not to hyaluronan. CONCLUSIONS: The cell surface antigen CD44 was expressed ubiquitously by LECs. Expression of its ligand hyaluronan by proliferating LECs suggests that this glycosaminoglycan may be important in the development of posterior capsule opacification.

Adult↗

Degenerated lens epithelial cells in rabbit and human eyes after intraocular lens implantation.

PURPOSE: To evaluate the role of lens epithelial cells (LECs) in posterior capsule opacification. SETTING: Departments of Ophthalmology and Pathology, Wakayama Medical College, Department of Anatomy, Kansai Shinkyu College, and Department of Ophthalmology, Kobe Kaisei Hospital, Japan. METHODS: We examined the presence of degenerated LECs on the capsules of the eyes of rabbits and a patient after intraocular lens (IOL) implantation. Phacoextraction of a crystalline lens and IOL implantation were done in 5 albino rabbits under general anesthesia. The animals were killed after 2 months. Lens capsules were removed and fixed. During vitreous surgery, a lens capsule with an IOL was removed from a patient. Ultrathin sections of specimens were studied by transmission electron microscopy. RESULTS: Presumed LECs proliferated between the posterior capsule and the IOL in association with collagenous matrix. Debris from the degenerated cells and destroyed intracellular organelles was also seen. CONCLUSION: Lens epithelial cells proliferating on the posterior capsule cannot survive indefinitely.

Aged↗

Recombinant TIMP-1 and -2 enhance the proliferation of rabbit corneal epithelial cells in vitro and the spreading of rabbit corneal epithelium in situ.

PURPOSE: The repair of the corneal epithelium is modulated by matrix metalloproteinases. The present study examined the effects of recombinant (r-) tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and -2) on the proliferation of cultured epithelial cells from rabbit cornea, and on the spreading of a sheet of squamous epithelium of rabbit cornea placed in an organ culture system. METHODS: DNA synthesis of the cells, with or without r-TIMPs, was determined by an immunoassay for BrdU incorporation. Cell proliferation was assayed by measuring MTT mitochondrial activity. Epithelial spreading was evaluated by culturing small corneal blocks for 24 h in the presence or absence of each agent. Cryosections were prepared and the epithelial growth on the cut stromal surface was measured. RESULTS: Each agent, r-TIMP-1 (at 50 and 100 ng/ml) and r-TIMP-2 (at 50 ng/ml) significantly enhanced the DNA synthesis and MTT activity of the corneal epithelial cells in vitro. Relative to the untreated control cells, DNA synthesis was increased 2.4-fold by r-TIMP-1 and 2.3-fold by r-TIMP-2. r-TIMP-1 (at 100 and 200 ng/ml) and r-TIMP-2 (at 10 and 50 ng/ml) each significantly enhanced the spreading of the corneal epithelium. Relative to the untreated control tissue, spreading of the epithelial sheet was increased 1.7-fold by r-TIMP-1 and 1.4-fold by r-TIMP-2. Higher concentrations of r-TIMP-1 and r-TIMP-2 did not further enhance either the DNA synthesis of the cultured cells or the spreading of the epithelium. CONCLUSIONS: Exogenous TIMPs enhanced the spreading of the corneal epithelium and proliferation of cultured corneal epithelial cells. Findings suggest that endogenous TIMPs may influence the healing of corneal epithelium in vivo.

Animals↗

Ultrastructural examination of corneal epithelium of spontaneously obese, hyperglycemic rats.

PURPOSE: Otsuka Long-Evans Tokushima fatty (OLETF) rats spontaneously become obese and hyperglycemic with age. We investigated whether the development of hyperglycemia would alter the ultrastructure of the corneal epithelium. METHODS: Scanning and transmission electron microscopy (SEM and TEM) were used to examine the morphology of corneal epithelial cells. Fourteen OLETF rats were evaluated, and 9 Long-Evans Tokushima Otsuka (LETO) rats were used as control. Non-hyperglycemic OLETF rats served as controls. RESULTS: SEM showed exfoliative changes in the surface of the central corneal epithelium of the hyperglycemic OLETF rats. These superficial epithelial cells were irregular in shape as compared to polygonal shapes of those of LETO and non-hyperglycemic OLETF rats. The mean anterior surface area of individual superficial epithelial cells was significantly smaller in the hyperglycemic OLETF than that of the LETO or the non-hyperglycemic OLETF rats. Central protrusion(s) could be found in some of the superficial cells of all rats examined, although this phenomenon was more common in the hyperglycemic rats than in the non-hyperglycemic rats. TEM revealed that there were numerous cytoplasmic vacuoles and wide intercellular spaces in the central corneal epithelium of the hyperglycemic OLETF rats, but not in the non-hyperglycemic rats. CONCLUSIONS: The development of spontaneous hyperglycemia in OLETF rats alters the ultrastructure of the corneal epithelium. The alterations included abnormalities of the corneal epithelial surface observed by SEM and the presence of intracellular vacuoles and enlarged intercellular spaces detected by TEM.

Animals↗

OPC-15161 suppresses the proliferation of Tenon's capsule fibroblasts and the production of type I collagen and fibronectin stimulated by TGF-beta1 in vitro.

PURPOSE: We investigated the effects of OPC-15161 on the growth of cultured human Tenon's capsule fibroblasts (TCFs), as well as on the production of type I procollagen, fibronectin, and laminin. These effects were examined in the presence or absence of TGF-beta1. METHODS: Cell proliferation was assayed by counting cell number and assay of DNA synthesis. Cytotoxicity was determined by the MTT method. Matrix components were assayed by enzyme immunoassay of material in the medium and in the cell lysate with or without OPC-15161. Total protein content was determined. Cellular ultrastructure was also evaluated. RESULTS: Treatment with OPC-15161 (up to 100.0 microg ml(-1)) significantly reduced the proliferation and DNA synthesis of TCFs. No significant decrease in MTT values was observed in confluent TCF cultures with OPC-15161 (up to 100.0 microg ml(-1)). TGF-beta1 enhanced the TCF production of procollagen I and fibronectin. OPC-15161 significantly decreased the procollagen I content in both the medium, in the cell lysate of TGF-beta1-stimulated cells, and fibronectin content in the lysate. OPC-15161 did not affect the laminin or total protein content, either with or without TGF-beta1. No ultrastructural evidence of cytotoxicity was observed. CONCLUSIONS: OPC-15161 inhibited the proliferation of TCFs, and reduced their production of procollagen I and fibronectin in the presence of TGF-beta1 without evidence of cytotoxicity. OPC-15161 may be useful in inhibiting the excessive fibrosis produced in the wound in response to filtering surgery.

Adult↗

Immunolocalization of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human subconjunctival tissues.

PURPOSE: To evaluate the roles of fibroblast proteins in the remodeling of the subconjunctival connective tissue, we immunohistochemically assessed the expression of matrix metalloproteinases (MMP)-1 and -2, and the tissue inhibitors of matrix metalloproteinases (TIMP)-1 and -2 in cultured human subconjunctival fibroblasts and in normal and healing human subconjunctival connective tissue. METHODS: Cultured fibroblasts derived from human subconjunctival connective tissue and surgical specimens of normal and healing conjunctiva were immunostained with monoclonal antibodies directed against human MMPs and TIMPs and examined by light and electron microscopy. RESULTS: In the cultured fibroblasts, MMP-1 and TIMP-1 antibodies stained the cytoplasm in a fine granular pattern, suggesting localization of those proteins in the endoplasmic reticulum (ER) and Golgi apparatus. Antibodies to MMP-2 and TIMP-2 reacted with fibroblast cytoplasm in a granular pattern. Electron microscopy of those fibroblasts revealed MMP-1 and TIMP-1 immunoreactivity in the ER cisternae or on the membrane of the ER. In surgical samples, MMP-1 and TIMP-1 were immunohistochemically detected in healing subconjunctival tissue, but not in conjunctival epithelium or normal subconjunctival tissue. CONCLUSIONS: MMPs and TIMPs may be involved in remodeling of subconjunctival connective tissue and in fibroblast population after surgical interventions. These proteins may play a crucial role in the post-operative fibrotic process occurring during scar formation in subconjunctival tissue.

Adult↗