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)

We have studied the effect of a specific FGF receptor suicide antagonist on the growth of bovine epithelial cells (BEL cells) in culture. This basic fibroblast growth factor-saporin conjugate (bFGF-SAP) has a biphasic effect on bovine lens epithelial cells (BEL cells). Whereas 0.01 nM and 0.1 nM bFGF-SAP stimulate BEL cells proliferation, 1 nM and 10 nM bFGF-SAP have the predicted toxic effects on BEL cell growth. The toxicity of bFGF-SAP is observed 2 to 3 days after the initial treatment and depends on cell density. Accordingly, the sensitivity of confluent cells to bFGF-SAP is reduced compared to sparse cells. A time course analysis reveals that bFGF-SAP is effective after a short exposure to cells and that its effects are not increased with longer treatments. Cell growth on bFGF-SAP pretreated extracellular matrix (ECM) or posterior lens capsule (PLC) is also affected. Basic FGF-SAP has been shown to bind to the extracellular material, allowing a modulation of lens cells migration and survival by a single treatment in vitro. This finding raises the possibility of its use in vivo to prevent capsules invasion by lens cells after cataract surgery.
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PMID:Biphasic effect of the mitotoxin bFGF-saporin on bovine lens epithelial cell growth: effect of cell density and extracellular matrix. 144 11

It has been reported that basic fibroblast growth factor (b-FGF) accelerates proliferation of mesenchymal cells and epithelial cells of cornea and crystalline lens in vitro. The immunohistochemical localization of b-FGF on guinea pig lens capsule after extracapsular extraction (ECE) of the lens was studied in order to investigate the role of b-FGF on posterior capsular opacification after ECE and neovascularization. On the 12th postoperative day, immunohistochemical staining of b-FGF was recognized along the posterior capsule on the cortical side, but not along the anterior capsule. On non-operated eyes, scanty immunoreactive materials were seen in cells at the germinative center of the equatorial region. More than two months after ECE, almost no immunoreactive staining could be recognized. In this study, immunoreactive staining of b-FGF was recognized along the posterior capsule on cortical side after operation. It has also been reported that b-FGF stimulates proliferation of the lens epithelial cells in vitro. Therefore, it is suggested that b-FGF plays an important role on posterior capsular opacification after cataract formation.
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PMID:[The change in immunohistochemical localization of basic fibroblast growth factor (b-FGF) around the lens capsule after extracapsular extraction]. 171 52

With regard to diabetic retinopathy, in addition to the demonstration by the DCCT study that prevention is achieved by good metabolic control, our present knowledge on physiopathology leads us to imagine three types of possible therapeutic approach; inhibition of glucotoxicity, improvement of capillary flow, blockade of angiogenesis. 1) Inhibition of glucotoxicity Aldose reductase inhibitors can prevent cataract in diabetic or galactosemic rats. The effect of these drugs on retinopathy, evaluated in some clinical trials, remains controversial, suggesting a minor role. Aminoguanidine is an inhibitor of formation of advanced glycosylation end-products (AGE). This compound has been tested on a model of experimental retinopathy in rats. Parallel to the AGE decrease in retina, formation of microaneurysms and loss of endothelial cells in capillaries were delayed. Clinical tolerance allows human application and randomised trials will give further information on this potentially efficient drug. 2) Improvement of capillary flow This objective can be obtained by drugs inhibiting platelet aggregation or improving erythrocyte or leucocyte deformability. Clinical trials using such compounds were not very conclusive. 3) Blockade of angiogenesis Proliferation of new vessels is a rather severe stage of diabetic retinopathy. Angiogenesis is due to factors locally produced (as FGF, TGF and u-PA produced by anoxic tissues), systemic (IGF-1) or released by inflammatory reaction (IL1, TNF alpha and beta). One imagines usage of drugs which inhibit these factors and prevent angiogenesis. At the present time, two approaches have been used in proliferative retinopathy worsening despite panphotocoagulation; analogues of somatostatin and interferon alpha. The promissing results of these pilot studies have to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Outlook for the future in the treatment of diabetic retinopathy]. 752 51

Basic fibroblast growth factor (bFGF) has been implicated as a factor in retinal differentiation and disease. Recent studies have shown that subretinal or intravitreal injections of bFGF delay the retinal degeneration of the RCS rat but the global nature of this effect has been quantified for few test animals and the mechanism underlying this effect is not understood. In order to determine more accurately the global effects of intravitreal bFGF and to further elucidate the mechanism of bFGF promoted photoreceptor cell saving, we injected one of three bFGF doses into the vitreal cavities of young RCS rats. Using measurements from several eyes, we confirmed that a single intravitreal bFGF injection globally delays the RCS dystrophy. Test eyes contained fewer debris zone macrophages and more inner retinal macrophages than did control eyes at 1 month post injection. As bFGF's saving effect waned, the number of inner retinal macrophages decreased and the number of debris zone macrophages increased toward control levels. Dose-dependent cataract formation occurred in 100% of test eyes. Eyes that received the highest bFGF dose showed increased retinal vascularization at 1, 2 and 3 months post injection. The possible relationships between bFGF promoted photoreceptor survival and our findings are discussed.
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PMID:The effects of bFGF on RCS rat eyes. 758 5

Spindle-shaped myofibroblast-like cells, which contain alpha-smooth muscle actin, have been described in anterior subcapsular cataract and after-cataract. In a previous study in this laboratory, it was shown that transforming growth factor-beta (TGF beta) induces the formation of spindle-shaped cells in lens epithelial explants. The aim of this investigation was to determine whether these TGF beta-induced spindle-shaped cells contain alpha-smooth muscle actin. Lens epithelial explants were prepared from 21-day-old rats and cultured with either TGF beta 1 or basic FGF alone, a combination of both growth factors, or without added growth factors. After three days, cellular changes were monitored by phase contrast microscopy, localisation of filamentous actin with rhodamine-phalloidin, and immunolocalisation and immunoblotting of alpha-smooth muscle actin. TGF beta induced rapid cell elongation and formation of characteristic spindle-shaped cells in lens epithelial explants in the presence or absence of FGF. These cells contained alpha-smooth muscle actin, a marker for myofibroblastic cells and a protein not normally found in the lens. The present study thus provides molecular evidence that TGF beta induces cataractous changes in lens epithelial cells. As TGF beta is potentially available to lens cells in situ throughout life, these findings are consistent with a key role for TGF beta in the aetiology of major forms of subcapsular cataract.
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PMID:TGF-beta 1 induces lens cells to accumulate alpha-smooth muscle actin, a marker for subcapsular cataracts. 772 Mar 96

TGF alpha, a member of the epidermal growth factor family stimulates proliferation of various cells. In the search for molecules that regulate cell division in the lens epithelium, the effect of numerous growth factors including EGF and FGF has been determined. In this study, the effect of TGF alpha on lens epithelial cells (LEC) from rabbit and monkey was investigated and compared to FGF and EGF. Since TGF alpha is suggested to be a factor that is regulated by auto and/or paracrine mechanisms, an immunohistochemical visualisation of the factor in the rabbit lens in situ was performed. TGF alpha stimulates LEC in a dose-dependent manner with a maximal threefold increase in cellular proliferation at 100 ng/ml. At a concentration above 10 ng/ml the cells lost their epithelial morphology and became irregular and star-shaped. Since TGF alpha is a potent LEC mitogen and has shown to increase in aqueous humour after trauma to the eye, this factor might be one of the molecules that regulate normal cell division in the ocular lens as well as LEC growth after cataract surgery.
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PMID:The effect of transforming growth factor-alpha (TGF alpha) on rabbit and primate lens epithelial cells in vitro. 813 35

Basic fibroblast growth factor (bFGF) and transforming growth factor alpha (TGF alpha) in rabbit aqueous humor were quantified before and after phacoemulsification (phaco) and intraocular lens (IOL) implantation by enzyme linked immunosorbent assay (ELISA). bFGF was not detected (< 10 pg/ml) before the operation, but increased to 250 +/- 150 pg/ml in a phaco group and 300 +/- 280 pg/ml in a phaco+IOL group on the first postoperative day. The concentration of bFGF in the aqueous humor was the highest in the first postoperative week, with a peak value of 390 +/- 180 pg/ml, and then gradually decreased to 130 +/- 50 pg/ml in the phaco group and 180 +/- 160 pg/ml in the phaco+IOL group in the eighth postoperative week. TGF alpha was not detected (< 10 pg/ml) before the operation or on the first postoperative day in either group. 25 +/- 50 pg/ml and 35 +/- 100 pg/ml of TGF alpha was detected in a phaco group and a phaco+IOL group on the third postoperative day and then TGF alpha in the aqueous humor gradually decreased becoming undetectable in the third postoperative week. The level of bFGF and TGF alpha was higher in a phaco+IOL group than in a phaco group but there was no statistical significance. The results show that bFGF increases in the aqueous humor for several postoperative weeks and suggests that it is one the of factors that promote capsular opacities and shrinkage in the early postoperative period of cataract extraction.
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PMID:[Quantification of basic fibroblast growth factor (bFGF) and transforming growth factor (TGF alpha) in rabbit aqueous humor after intraocular lens implantation]. 816 63

Posterior capsule opacification (PCO) is the most frequent complication associated with decreased vision after cataract surgery. Previous methods of preventing PCO have not proven to be practical, effective, and safe for routine clinical procedure, but some novel concepts and methods have recently been developed. This 2-part review looks at clinical and experimental investigations of PCO, focusing on developments since 1992. Clinical aspects will be presented in a later issue. This paper addresses (1) in vitro models for PCO research; (2) pathophysiology and molecular biology of lens epithelial cells (LECs); (3) prevention of PCO. Of special interest are methods of culturing human LECs obtained by capsulotomy during cataract surgery, including those obtained with an intact capsular bag, to provide an in vitro model for investigating the pathophysiology of LECs; the effect of a sharp bend in the lens capsule that induces contact inhibition of migrating LECs; more specific inhibition of migrating LECs using an immunotoxin, b-FGF-saporin, or EDTA and RGD-peptides.
J Cataract Refract Surg 1999 Jan
PMID:Posterior capsule opacification. Part 1: Experimental investigations. 988 86

TGFbeta induces changes characteristic of some forms of cataract. However, the responsiveness of lens epithelial cells to TGFbeta is age-dependent; weanling and adult, but not neonatal, lens epithelial cells respond. This study investigated TGFbeta receptor (TbetaRI and TbetaRII) expression during rat lens development and the effects of FGF-2 on TGFbeta responsiveness and TbetaR expression. Immunofluorescence, immunoblotting, RT-PCR and in situ hybridization were used to examine the spatio-temporal expression patterns of TbetaR. Lens explants were used to investigate the effects of FGF-2 on TGFbeta responsiveness and TbetaR expression. In the lens epithelium, little or no immunoreactivity was detected at P3 but at P21 there was distinct reactivity for TbetaRI and TbetaRII. Reactivity for both receptors was also found in the differentiating fibers in the transitional zone and cortex at both ages. Western blotting of lens membrane extracts identified multiple molecular weight forms of TbetaRI (30, 50, 90 kDa) and TbetaRII (70-120 kDa). In situ hybridization with a rat probe for Alk5 (TbetaRI) showed that the lens expresses Alk5 mRNA in epithelium and fibers throughout development. A rat TbetaRII probe revealed distinct expression of a TbetaRII mRNA in lens fibers throughout development and in the lens epithelium at P21 but not at P3. In vitro studies showed that lens epithelial explants from P9 rats did not undergo cataractous changes in response to TGFbeta but P13 explants did. Addition of FGF-2 to P9 explants induced increased TbetaR immunoreactivity and enhanced the competency of lens epithelial cells to respond to TGFbeta. These data indicate that the overall increased expression of TGFbeta receptors in lens epithelium during postnatal development (P3-P21) underlies an age-related change in TGFbeta responsiveness. The results also suggest that lens cells may express multiple forms of TbetaR. Expression of TbetaR in lens fibers throughout lens development and the induction of enhanced TbetaR expression by FGF suggest a role for TGFbeta signaling during FGF-induced responses and fiber differentiation.
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PMID:Tgfbeta receptor expression in lens: implications for differentiation and cataractogenesis. 1138 53

The heat shock transcription factor (HSF) family consists of three members in mammals and regulates expression of heat shock genes via a heat shock element. HSF1 and HSF2 are required for some developmental processes, but it is unclear how they regulate these processes. To elucidate the mechanisms of developmental regulation by HSFs, we generated mice in which the HSF4 gene is mutated. HSF4-null mice had cataract with abnormal lens fiber cells containing inclusion-like structures, probably due to decreased expression of gamma-crystallin, which maintains protein stability. Furthermore, we found increased proliferation and premature differentiation of the mutant lens epithelial cells, which is associated with increased expression of growth factors, FGF-1, FGF-4, and FGF-7. Unexpectedly, HSF1 competed with HSF4 for the expression of FGFs not only in the lens but also in other tissues. These findings reveal the lens-specific role of HSF4, which activates gamma-crystallin genes, and also indicate that HSF1 and HSF4 are involved in regulating expression of growth factor genes, which are essential for cell growth and differentiation.
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PMID:HSF4 is required for normal cell growth and differentiation during mouse lens development. 1548 28


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