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)

Explanted newborn rat lens epithelial cells were cultured with various concentrations of FGF-2 and/or insulin or IGF-I for 8-20 days. The accumulation of alphaA-, alphaB-, betaA3/1-, betaB2- and gammaA-F-crystallin was measured. During culture with insulin only, i.e. in the absence of fibre cell differentiation, alphaA- and alphaB-crystallin accumulated to the same level as found in differentiating cells. Culture of epithelial cells with IGF-I led to an increase in alphaB-crystallin, but not in alphaA-crystallin. The addition of insulin under differentiation conditions (in the presence of 25 ng ml(-1)FGF-2) augmented the accumulation of alphaA-crystallin 1.5-fold, the accumulation of betaB2-crystallin two-fold and the accumulation of gammaA-F-crystallin five-fold over that found with FGF-2 only. The accumulation of alphaB- and betaA3/1-crystallin was not affected by insulin in the presence of FGF-2. Adding IGF-I to fibre cells differentiating in the presence of 25 ng ml(-1)FGF-2 resulted in a 1.5-fold increase (of questionable statistical significance) in both alphaA- and alphaB-crystallin and a two to three-fold increase in gammaA-F-crystallin compared to cells cultured with FGF-2 only, no significant effect of IGF-I on the accumulation of betaA3/1- or betaB2-crystallin was found. Comparison of the levels of mRNA and protein suggests that insulin acts to increase the level of transcription. Our results show that the response of fibre cells to insulin or IGF-I differs. Hence, even though half the maximum dosage required for the insulin effect was rather high (between 0.1 and >5 micro g), the effect of insulin cannot be merely transmitted by the IGF-I receptor. Our data further predict that insulin or IGF-I increases the overall ratio of beta- and gamma-crystallin to alpha-crystallin in the fibre cell, which could predispose the lens to cataract.
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PMID:Insulin and IGF-I affect the protein composition of the lens fibre cell with possible consequences for cataract. 1084 83

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

Following cataract surgery, many patients suffer secondary loss of vision because of posterior capsule opacification (PCO), which arises when residual lens epithelial cells become aberrant and migrate into the light path. Transforming growth factor-beta (TGFbeta)-induced transdifferentiation of lens cells appears to play a key role in this process. Fibroblast growth factor (FGF) may also play a role by promoting the survival of TGFbeta-affected cells and influencing their subsequent behaviour. In the present study, the effects of two different TGFbeta and FGF treatment regimes were compared in rat lens epithelial explants with either low or high initial cell coverage. Explants treated with 50 pg ml(-1) TGFbeta2 and 20 ng ml(-1) FGF-2 sequentially (day 0, day 1) or simultaneously (day 0), then cultured for up to 30 days with FGF, were assessed by light microscopy and immunolocalisation of markers for transdifferentiation (alpha-smooth muscle actin (alphaSMA) and type I collagen) or lens epithelial phenotype (Pax6) and fibre differentiation (beta-crystallin). By day 4, most cells had lost Pax6 reactivity, alphaSMA reactivity was evident, and there were differences between growth factor treatment groups, low and high initial cell coverage explants, and peripheral and central regions of explants. On day 30 of culture, all explants were well populated with cells, irrespective of treatment and initial cell coverage, and exhibited diverse PCO-like morphological changes, with expression of transdifferentiation markers and beta-crystallin in virtually all cells. Such overall resilience to variations in conditions may contribute to the insidious nature of PCO, while factors related to observed early differences between groups may contribute to PCO pleiomorphism.
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PMID:Posterior capsule opacification-like changes in rat lens explants cultured with TGFbeta and FGF: effects of cell coverage and regional differences. 1635 63

Posterior capsular opacification (PCO) arises from lens cells that remain associated with the lens capsule after cataract surgery and subsequently become abnormal, proliferate and migrate into the visual pathway. In this study, a rat lens explant model was used to assess the effects of the prototype steroidal and non-steroidal anti-inflammatory drugs, dexamethasone (DEX) and diclofenac (DIC), on epithelial cells undergoing PCO-like changes. Such drugs are widely used at the time of cataract surgery. TGFbeta2 and FGF-2 were added sequentially and explants were cultured for up to 30 days, with or without addition of DEX or DIC at a clinically relevant concentration. Without DEX or DIC, explants became multilayered and cells tended to retract into PCO-like plaques. Inclusion of DEX, but not DIC, resulted in transient formation of needle-like cells, enhanced cell coverage, and the retention a monolayer of migratory cells surrounding PCO-like plaques. With or without drug addition, most cells became aberrant, as indicated by loss of Pax6 expression and the presence of PCO markers alpha-smooth muscle actin and type I collagen; however, DEX and DIC both strongly enhanced type I collagen accumulation. Furthermore, DEX enhanced cell coverage in explants treated with TGFbeta alone. Thus the behaviour of lens cells was significantly and differentially affected by the presence of DEX and DIC, highlighting the possibility that drugs used to control inflammation after cataract surgery, and the clinician's choice of drugs, may influence PCO development.
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PMID:Differing effects of dexamethasone and diclofenac on posterior capsule opacification-like changes in a rat lens explant model. 1671 96