Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Immunolocalization of prolyl 4-hydroxylase subunits, alpha-smooth muscle actin, and extracellular matrix components in human lens capsules with lens implants. 953 56

In this study, lenses of autopsy eyeballs, anterior capsules including lens epithelium taken during operation for cortical cataract, after cataract tissue obtained at the time of operation, and Elschnig's pearles and Soemmerring's ring from autopsy eye-balls were examined for a variety of factors, such as growth factors, cytokines, bioactive substance factors, cytoskeleton proteins and extracellular matrices by immunocytohistochemistry. Preoperative lens epithelium expressed epidermal growth factor (EGF), EGF-receptor (R), fibroblast growth factor (FGF), FGF-R, interleukin (IL)-1-RII, tumor necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor type-1 (PAI-1), keratin and laminine. In addition to the above factors, opacified fibrous capsule in after cataract expressed transforming growth factor-beta (TGF-beta), insulin-like growth factor-II (IGF-II), platelet derived growth factor-AB (PDGF-AB), IL-6, prostaglandin-E2 (PG-E2), alpha smooth muscle actin, fibronectin, and I and III to VI type collagen. Elschnig's pearls expressed FGF-R, TNF-alpha, and laminin. Soemmerring's ring expressed EGF, FGF, FGF-R, IL-1-RII, keratin, tissue-PA, and PAI-1.
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PMID:[Immunohistochemical studies on factors involved in after cataract]. 975 25

The lens capsule and silicone intraocular lens (IOL) extracted from the eye of a patient with chronic infectious endophthalmitis was examined histopathologically to evaluate the pathology of a capsule and IOL surfaces in the presence of bacterial infection. A 69-year-old man developed an infection in his right eye 4 months after phacoemulsification and aspiration of a cataract and implantation of a silicone IOL. During vitrectomy, the capsule and IOL were extracted and processed for light or scanning electron microscopy. Cryosections of the capsule were subjected to Gram staining and immunohistochemical tests for extracellular matrix components. The lens capsule contained an accumulation of extracellular matrix, including collagen types and fibronectin. A colony of Gram-positive rod bacteria was detected inside the capsular bag. Scanning electron microscopy failed to detect any microorganisms on the IOL surface. Histological examination of cryosections of the extracted capsule confirmed the presence of infection during surgery even though preoperative cultures of intraocular fluid were negative. Immediate antibacterial treatment could be initiated.
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PMID:Pathological findings in lens capsule and silicone intraocular lens extracted from eye with chronic infectious endophthalmitis. 988 35

Cataract formation is a deleterious side effect of some hormone therapies, thus, it is important to understand how hormones regulate lens basement structure and function. We have examined the effects of dexamethasone (DEX) on the regulation of Secreted Protein Acidic and Rich in Cysteines (SPARC), fibronectin (FN), and collagen IV (CN IV). To radiolabel newly synthesized proteins, cultured monolayers of bovine anterior lens capsule epithelial (ALCE) cells were pulsed with [(3)H] proline. To identify proteins, an immunofluorescent technique, immunoprecipitation with specific antibodies, and electrophoretic separation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used. DEX increased production of total proteins, whereas it specifically decreased synthesis of FN and CN IV. A decrease in FN and CN IV synthesis by DEX in ALCE cells may decrease adhesion of lens epithelium to the basement membrane (BM), which may in turn cause pathogenesis. Messenger RNAs were identified by Northern blot analyses using specific DNA probes. Treatment of lens epithelial cells with DEX causes a 100-150% up-regulation of SPARC mRNA in a concentration-dependent fashion. The increase in the expression of FN mRNA by DEX was in a dose-response fashion and varied from 50-600%. A 24-hour treatment with DEX (10(-6)M) increased CN IV mRNA levels to 386% over baseline levels. Thus showing a differential upregulation by DEX of mRNAs of SPARC, FN, and CN IV. Results of nuclear run-on transcription assays indicate that regulation of RNAs by DEX may occur, in part, at the transcriptional level. The aberrant expression of lens basement membrane proteins by DEX may contribute to abnormal lens cell function and ultimately to anterior subcapsular cataract.
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PMID:Expression and regulation of SPARC, fibronectin, and collagen IV by dexamethasone in lens epithelial cells. 1246 89

We report the histological findings in posterior capsule opacification (PCO) in 2 eyes of a 10-month-old infant 8 months after cataract extraction and intraocular lens (IOL) implantation. The PCO in the right eye had a regenerated lenticular structure; in the left eye, it was fibrotic. The PCO in the right eye was soft and aspirated with Simcoe's irrigation/aspiration cannula; in the left eye, it was excised surgically. Paraffin sections of the fibrous PCO tissue from the left eye were examined histologically. Hematoxylin-eosin staining showed extracellular matrix (ECM) accumulation and the presence of elongated fibroblastic cells, presumed to be lens epithelial cells (LECs). Immunohistochemistry revealed the presence of fibrous collagen types and cellular fibronectin. The presumed LECs amid the ECM were positive for vimentin and alpha-smooth muscle actin. Histology of the fibrous PCO tissue from this infant was similar to that in adult patients.
J Cataract Refract Surg 2004 Feb
PMID:Histology and immunohistochemistry of fibrous posterior capsule opacification in an infant. 1503 Aug 55

We investigated whether amyloid beta(Abeta) aggregates have transforming growth factor beta- like cytokine activity and cause transdifferentiation of lens epithelial cells, leading to certain types of cataract. In order to mimic Abetaaggregates, Abeta-(1-40) was crosslinked to bovine serum albumin (BSA) with disuccinimidyl suberate according to a previously described procedure. When human lens epithelial B-3 (HLE B-3) cells were treated with the Abeta-(1-40)-BSA conjugates, we observed the translocation of Smad-3, as well as the induced mRNA levels of fibronectin (FN), collagen type I (Col I), smooth muscle actin (SMA) and matrix metalloproteinase-2 (MMP-2). In addition, we investigated the morphology of rat whole lens cultured for 5 days in the presence of Abeta-(1-40)-BSA, and the immunohistochemical localizations of Abeta-(1-40)/amyloid precursor protein (APP) in human clinical tissues beneath the anterior capsules. In rat whole lens cultures, treatment with Abeta-(1-40)-BSA produced a transformed morphology that had multiple layers of lens epithelial cells. To compare the anterior capsules in anterior subcapsular cataracts with those in nuclear cataracts, immunohistochemical studies of Abeta/APP in human clinical tissues revealed that the predominant immunostaining of Abeta occurs in the anterior epithelial plaques, which likely produces the abnormal extracellular matrix. Thus, these findings suggest that Abeta aggregates in vivo are possibly involved in the regulatory process by which lens epithelial cells may transdifferentiate into fibroblast-like cells, as well as help understand the mechanisms which lead to certain types of cataractogenesis.
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PMID:Possible role of amyloid beta-(1-40)-BSA conjugates in transdifferentiation of lens epithelial cells. 1511 92

A major complication of intraocular lens surgery is diminished visual acuity caused by the regrowth of lens epithelial cells (secondary cataract). Polymethylmethacrylate (PMMA) is a commonly used intraocular lens material. This study addresses the mechanisms underlying the initial adhesion of lens epithelial cells to PMMA and a functionalized PMMA-based terpolymer known to inhibit cell proliferation. Rabbit lens epithelial cells were cultured on the test polymer surfaces in medium containing serum depleted of either fibronectin or vitronectin (or both) to identify the role of these proteins in the initial process of cell adhesion. Adherent cells were quantitated after 60 min, and the actin cytoskeleton and focal contact formation were compared in each serum treatment on both polymers. Vitronectin was significantly more effective for initial cell attachment to both polymers than fibronectin. Normal cell spreading on PMMA required vitronectin and was independent of fibronectin, whereas cell spreading on the terpolymer was abnormal and required the presence of fibronectin and vitronectin together. Together, these results help to explain the inhibition of cell proliferation previously shown on the functionalized PMMA. This work contributes to the design of a polymer for use in intraocular lenses that inhibits proliferation of the target cells.
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PMID:Vitronectin is significant in the adhesion of lens epithelial cells to PMMA polymers. 1512 94

We report the histological finding of complete closure of the anterior capsulotomy window in 2 cases. The cases were successfully treated with surgery after neodymium:YAG laser anterior capsulotomy failed. Histology and immunohistochemistry were performed to determine the pathogenesis. Histology revealed the presence of elongated, fibroblast-like lens epithelial cells in association with extracellular matrix accumulation, which were positive for collagen types, fibronectin, and osteopontin. The cells were labeled with anti-alpha-smooth muscle actin antibody. The finding indicates that phenotypic modulation in lens epithelial cell to contractile cell type and accumulation of matrix are involved in closure of the anterior capsulotomy window.
J Cataract Refract Surg 2004 Jun
PMID:Histological observation of complete closure of anterior capsulotomy in 2 cases. 1517 21

The vertebrate lens has a distinct polarity and structure that are regulated by growth factors resident in the ocular media. Fibroblast growth factors, in concert with other growth factors, are key regulators of lens fiber cell differentiation. While members of the transforming growth factor (TGFbeta) superfamily have also been implicated to play a role in lens fiber differentiation, inappropriate TGFbeta signaling in the anterior lens epithelial cells results in an epithelial-mesenchymal transition (EMT) that bears morphological and molecular resemblance to forms of human cataract, including anterior subcapsular (ASC) and posterior capsule opacification (PCO; also known as secondary cataract or after-cataract), which occurs after cataract surgery. Numerous in vitro and in vivo studies indicate that this TGFbeta-induced EMT is part of a wound healing response in lens epithelial cells and is characterized by induced expression of numerous extracellular matrix proteins (laminin, collagens I, III, tenascin, fibronectin, proteoglycans), intermediate filaments (desmin, alpha-smooth muscle actin) and various integrins (alpha2, alpha5, alpha7B), as well as the loss of epithelial genes [Pax6, Cx43, CP49, alpha-crystallin, E-cadherin, zonula occludens-1 protein (ZO-1)]. The signaling pathways involved in initiating the EMT seem to primarily involve the Smad-dependent pathway, whereby TGFbeta binding to specific high affinity cell surface receptors activates the receptor-Smad/Smad4 complex. Recent studies implicate other factors [such as fibroblast growth factor (FGFs), hepatocyte growth factor, integrins], present in the lens and ocular environment, in the pathogenesis of ASC and PCO. For example, FGF signaling can augment many of the effects of TGFbeta, and integrin signaling, possibly via ILK, appears to mediate some of the morphological features of EMT initiated by TGFbeta. Increasing attention is now being directed at the network of signaling pathways that effect the EMT in lens epithelial cells, with the aim of identifying potential therapeutic targets to inhibit cataract, particularly PCO, which remains a significant clinical problem in ophthalmology.
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PMID:Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens: a model for cataract formation. 1594 92

Posterior capsule opacification (PCO) after cataract surgery is caused by growth of residual human lens epithelial (HLE) cells on the posterior capsule. We have shown that extracellular matrix (ECM) is an essential factor for HLE cell attachment and migration. The purpose of this study was to examine the inhibitory effects of Arg-Gly-Asp (RGD) peptide on cell attachment and migration in an HLE cell line. HLE cell line cells (SRA 01/04) that were obtained by transfection of large T antigen of SV40 were cultured in the absence of serum. The culture dishes were coated with type IV collagen, laminin or fibronectin, and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) RGD peptide (0.1, 0.3, 1.0, 2.0 mg/ml) was added to the medium. The number of attached cells was counted after 90 min of incubation, and the inhibitory effects of GRGDSP RGD peptide on cell attachment were calculated. Cell attachment on the fibronectin-coated dishes was inhibited by GRGDSP RGD peptide at concentrations higher than 0.3 mg/ml; the inhibitory rate was 80% at a concentration of 2.0 mg/ml. The inhibition of cell attachment by GRGDSP RGD peptide on laminin-coated dishes appeared only at a concentration of 2.0 mg/ml, whereas no effects were observed on the type IV collagen-coated dishes. The inhibitory effects of GRGDSP RGD peptide on cell migration were measured in medium containing 2.0 mg/ml of GRGDSP RGD peptide after 1, 3, 5 and 7 days of culture. Cell migration was inhibited by GRGDSP RGD peptide from 1 day of culture on the fibronectin-coated dishes and from 5 days of culture on the laminin-coated dishes, whereas no effects were observed on the type IV collagen-coated dishes. GRGDSP RGD peptide inhibited cell attachment and migration on laminin and fibronectin that have RGD sequences. These data suggested that RGD peptide may have the potential to prevent PCO.
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PMID:Inhibitory effects of Arg-Gly-Asp (RGD) peptide on cell attachment and migration in a human lens epithelial cell line. 1599 Apr 62


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