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)

Characteristic lens epithelial cell behavior in the pseudophakic eye was examined by comparing 30 eyes that had extracapsular cataract surgery by the intercapsular technique and posterior chamber intraocular lens (IOL) implantation with lens epithelial cell removal but without anterior capsule capsulectomy and nine aphakic eyes that had the same procedure but without posterior chamber lens implantation over a mean follow-up period of 30 and 23 months, respectively. Fibrous anterior capsule opacification was observed in 83% of the pseudophakic eyes in the area of contact with the IOL, while the region beyond the margin of the IOL remained transparent. Fibrous anterior capsular opacification was not noted in the aphakic eyes. This suggests that the IOL material, poly(methyl methacrylate), stimulates lens epithelial cells to undergo fibrous metaplasia and to produce collagen fibers. Various cytokines such as IL-1 and TGF-beta synthesized by lens epithelial cells may play a crucial role as mediators in the process. We recommend that this effect be considered as a parameter of biocompatibility in developing and evaluating new biomaterials.
J Cataract Refract Surg 1991 Jul
PMID:Intercapsular cataract surgery with lens epithelial cell removal. Part IV: Capsular fibrosis induced by poly(methyl methacrylate). 189 24

By using the highly sensitive and specific technique of enzyme-linked immunosorbent assay, we investigated the presence and amount of transforming growth factor-beta 2 (TGF-beta 2) in samples of aqueous humor obtained from 15 patients who had a clinically established diagnosis of advanced primary open-angle glaucoma (POAG), as well as from ten age-matched normal human subjects undergoing cataract surgery. The total amount of TGF-beta 2 in the samples of normal aqueous humor ranged from 0.41 to 2.24 ng ml-1 (mean +/- S.D.: 1.48 +/- 0.68 ng ml-1) of which 4.88 to 37.05% (11.99 +/- 9.95%) was intrinsically active. Compared with normal subjects, the aqueous humor from POAG patients had a statistically significantly greater amount of total TGF-beta 2 (2.70 +/- 0.76 ng ml-1, P < 0.01), as well as a higher level of intrinsically active TGF-beta 2 (0.45 +/- 0.28 ng ml-1, P < 0.05) which corresponded to 1.09 to 60.84% (18.33 +/- 15.50%) of the total amount. No linear correlation was found between the age of the subjects and the protein concentration of the aqueous humor from either normal or glaucomatous eyes, nor between the age of the patient and the total amount of TGF-beta 2. The negligible amount of TGF-beta 2 present in serum argues against its influx into the aqueous humor after breakdown of the blood-aqueous barrier that is known to occur in glaucomatous eyes; rather, our present findings support the concept of the intraocular derivation of this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. 769 65

Mature and total TGF-beta 2 levels were determined in normal human tears, from 37 volunteers, using a quantitative "sandwich' enzyme immunoassay technique. Since this ELISA method recognizes only mature TGF-beta 2, total TGF-beta 2 levels in tears were measured after acid activation. Aqueous humor samples from 9 patients with cataract were also tested as controls. Mature and total TGF-beta 2 in aqueous humor (AH) averaged 182 pg/ml and 737 pg/ml, respectively. The levels of mature TGF-beta 2 in normal human tears ranged from 36 to 71 pg/ml (mean: 55 pg/ml). And the levels of total TGF-beta 2 ranged from 3446 to 14910 pg/ml (mean: 7854 Pg/ml), a very high level. Percentage of mature TGF-beta 2 ranged 0.4 to 1.3% (mean: 0.9%). It is reported for the first time that there are very high levels of total TGF-beta 2 in normal human tears.
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PMID:High total TGF-beta 2 levels in normal human tears. 865 16

Cataract, already a major cause of visual impairment and blindness, is likely to become an increasing problem as the world population ages. In a previous study, we showed that transforming growth factor-beta (TGFP) induces rat lenses in culture to develop opacities and other changes that have many features of human subcapsular cataracts. Here we show that estrogen protects against cataract. Lenses from female rats are more resistant to TGFbeta-induced cataract than those from males. Furthermore, lenses from ovariectomized females show increased sensitivity to the damaging effects of TGFbeta and estrogen replacement in vivo, or exposure to estrogen in vitro, restores resistance. Sex-dependent and estrogen-related differences in susceptibility to cataract formation, consistent with a protective role for estrogen, have been noted in some epidemiological studies. The present study in the rat indicates that estrogen provides protection against cataract by countering the damaging effects of TGFbeP. It also adds to an increasing body of evidence that hormone replacement therapy protects postmenopausal women against various diseases.
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PMID:Estrogen protects lenses against cataract induced by transforming growth factor-beta (TGFbeta). 901 76

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

It has been demonstrated that exquisite regulation of the cell cycle between the activation and inhibition is crucial to maintain the transparency of the ocular lens. While it is generally recognized that the sugar cataract is accompanied by the enhanced proliferation of lens epithelial cells (LECs), it is unclear whether or not an inhibitory mechanism against the lens proliferation is involved, except for TGF-beta. In this study, the authors demonstrated the enhanced expression of p21(WAF-1/CIP-1), a potent inhibitor against cell cycle progression, and its specific temporal and regional expression profiles in the LECs during the development of sugar cataract. Sugar cataract was induced in 6-week-old male Sprague-Dawley rats by feeding them on a 50% galactose-rich diet, and then the expression patterns of p21(WAF-1/CIP-1) mRNA and protein with the advance of the sugar cataract were studied. Western blot analyses showed that p21(WAF-1/CIP-1) expression increased throughout the period of galactose exposure, up to 21 days. Also, a gradual increase in the number of p21(WAF-1/CIP-1) positive cells was observed immunohistochemically in the course of the galactose exposure. Interestingly, p21(WAF-1/CIP-1) was significantly expressed in the multi-layered epithelium, which was observed typically in the advanced cataract. Proliferating cell nuclear antigen (PCNA), an indicator of cell proliferation, was also positive in the most multi-layered epithelial cells. In addition, transient expression of PCNA mRNA and its protein was noticed throughout the lens epithelium in the course of the sugar cataract development. Prior to the elevation of p21(WAF-1/CIP-1) mRNA expression, PCNA mRNA expression increased greatly and reached a peak according to the semiquantitative analyses using either the real time reverse transcription-polymerase chain reaction (RT-PCR) or the Southern blot analyses. Based on these observations, it is possible that p21(WAF-1/CIP-1) is elevated and exerts its inhibitory action against the proliferating epithelial cells during the development of the sugar cataract.
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PMID:Increased expression of p21(WAF-1/CIP-1) in the lens epithelium of rat sugar cataract. 1195 Feb 35

Anterior subcapsular cataracts cause a serious loss of vision and are normally associated with ocular trauma, inflammation or clinical skin conditions. They appear to be accompanied by epithelial cell growth and transdifferentiation where unscheduled production of a number of proteins, including alpha smooth muscle actin (alpha-sma), occurs. Clinical studies have also revealed an up-regulation of the TGFbeta signalling pathway in such cataracts. The present study, using phase contrast and immunofluorescent techniques, was undertaken to investigate the extent of alpha-sma expression in traumatic cataracts, in capsulorhexis specimens obtained during cataract surgery and in aged human lenses from donor eyes. The donor lenses were also exposed to trauma or TGFbeta in culture to observe their relative contribution to alpha-sma production. Dense anterior subcapsular cataracts were relatively rare (<1%), but all showed a pronounced up-regulation of alpha-sma, which was located both in anterior cells of normal appearance and in nucleated fibroblastic cells lying beneath the anterior epithelium. Surprisingly, more than 50% of capsulorhexis specimens from mature cataracts showed expression of alpha-sma, although to a limited extent. Alpha-sma was not expressed in any of the clear donor lenses and culture for 8 days in EMEM did not induce expression. Interestingly, unlike their young animal counterparts, human lenses failed to show the presence of alpha-sma when exposed to 10 ng ml(-1) TGFbeta. However, after culture, lenses with pre-existing cortical opacities did express alpha-sma, as did clear lenses subjected to injury or trauma. It appears that the greater the stress, the greater is the expression of alpha-sma. Cataract, and especially cortical cataract, should therefore be seen as associated with stress-induced signalling pathways in the lens that lead to the transdifferentiation of the anterior epithelial cells.
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PMID:Epithelial transdifferentiation and cataract in the human lens. 1290 66

Lens epithelial cells undergo epithelial-mesenchymal transition (EMT) after injury as in cataract extraction, leading to fibrosis of the lens capsule. Fibrosis of the anterior capsule can be modeled in the mouse by capsular injury in the lens, which results in EMT of the lens epithelium and subsequent deposition of extracellular matrix without contamination of other cell types from outside the lens. We have previously shown that signaling via Smad3, a key signal-transducing element downstream of transforming growth factor (TGF)-beta and activin receptors, is activated in lens epithelial cells by 12 hours after injury and that this Smad3 activation is blocked by administration of a TGF-beta 2-neutralizing antibody in mice. We now show that EMT of primary lens epithelial cells in vitro depends on TGF-beta expression and that injury-induced EMT in vivo depends, more specifically, on signaling via Smad3. Loss of Smad3 in mice blocks both morphological changes of lens epithelium to a mesenchymal phenotype and expression of the EMT markers snail, alpha-smooth muscle actin, lumican, and type I collagen in response to injury in vivo or to exposure to exogenous TGF-beta in organ culture. The results suggest that blocking the Smad3 pathway might be beneficial in inhibiting capsular fibrosis after injury and/or surgery.
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PMID:Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury. 1474 69

The total transforming growth factor (TGF) beta(2) concentration in the anterior chamber aqueous humor of 96 cataract patients with ages ranging from 17 to 88 years was measured using ELISA to investigate the changes that occur with age, difference of axial length, difference of localization of opacification of the cataractous lens and complications with other eye diseases. It was found that the total TGF-beta(2) concentration (1) decreases with age, (2) shows slight changes with axial length, (3) has slight changes with difference of localization of opacification, (4) is significantly high in patients with concurrent open-angle glaucoma (p < 0.05), (5) is high in patients with complicating diabetes who have undergone panretinal photocoagulation for diabetic retinopathy (p < 0.05) and (6) is low in patients with atopic cataracts. There have been several reports on point 4 above, but none to date of the other points. These findings provide useful information on the intraocular activity of TGF-beta(2).
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PMID:Concentration of transforming growth factor beta2 in aqueous humor. 1563 19

Normal lens development and growth is dependent on the tight spatial and temporal regulation of lens cell proliferation and fiber cell differentiation. The present study reports that these same cellular processes contribute to lens pathology as they become deregulated in the process of anterior subcapsular cataract development in a transgenic mouse model. During the formation and growth of transforming growth factor (TGF)beta-induced subcapsular plaques, lens epithelial cells lose key phenotypic markers including E-cadherin and connexin 43, they multilayer and subsequently differentiate into myofibroblastic and/or fiber-like cells. Growth of the subcapsular plaques in the transgenic mouse is sustained by an ordered process of cell proliferation, exit from the cell cycle and differentiation. As reiterating ordered growth and differentiation patterns is atypical of the direct effects of TGFbeta on lens cells in vitro, we propose that other growth factors in the eye, namely fibroblast growth factor, may also play a role in the establishment and regulation of the key cellular processes leading to lens pathology. Obtaining a better understanding of the molecular aspects and cellular dynamics of cataract formation and growth is central to devising strategies for slowing or preventing this disease.
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PMID:Deregulation of lens epithelial cell proliferation and differentiation during the development of TGFbeta-induced anterior subcapsular cataract. 1585 73


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