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

Aggregation and covalent cross-linking of the crystallins, the major structural proteins of the eye lens, increase light scattering by the lens leading to opacification and cataract. Disturbance of calcium homeostasis in the tissue is one of the factors implicated in cataractogenesis. Calcium-activated transglutaminase (TG)-catalyzed cross-linking of some lens proteins has been reported earlier. We show here that alpha-crystallin, a major structural protein in the lens and a member of the small heat shock protein family, is also a substrate for TG-mediated cross-linking, indicating the presence of donor Lys and acceptor Gln residues in the protein. Upon TG-catalyzed dimerization, the secondary and tertiary structures of the protein are altered, and its surface hydrophobicity reduced. The chaperone-like property of the protein, suspected to be one of its functions in situ, is substantially reduced upon such cross-linking. These results, taken together with earlier ones on lens beta-crystallins and vimentin, suggest that TG-mediated events might compromise lens function. Also, since alpha-crystallin occurs not only in the lens but in other tissues as well, such TG-catalyzed cross-linking and the associated alterations in its structure and activity would be of general pathological interest.
 ...
PMID:Transglutaminase-mediated cross-linking of alpha-crystallin: structural and functional consequences. 1142 25

The possible role of ultraviolet light in the formation of cataract is not well understood. In this study, guinea pigs were exposed to a chronic, low level of UVA light (0.5 mWcm(-2), 340-410 nm wavelength, peak at 365 nm) for 4-5 months. It is known that the lens of the guinea pig possesses unusually high levels of the UVA chromophore NADPH. In a preliminary analysis, it was found that isolated guinea pig corneas transmitted 70-90% of 340-400 nm light, and that UVA radiation was able to penetrate deep into the nucleus of the guinea pig lens, where it was absorbed. Exposure of guinea pigs to UVA in vivo produced a 60% inactivation of lens epithelial catalase; however, analysis by transmission electron microscopy (TEM) showed no apparent morphological effects on either the lens epithelium or the cortex. A number of UVA-induced effects were found in the nucleus of the guinea pig lens, but were observed either not at all or to a lesser extent in the cortex. The effects included an increase in light scattering (two-fold; slit-lamp examination), distention of intercellular spaces (TEM), an increase in lipid peroxidation (30-35%; infrared spectroscopy), a decrease in GSH level (30%), an increase in protein-thiol mixed disulfide levels (80%), loss of water-soluble protein (20%), an increase in the amount of protein disulfide (two-fold; two-dimensional diagonal electrophoresis), degradation of MIP26 (15%) and loss of cytoskeletal proteins including actin, alpha- and beta- tubulin, vimentin and alpha-actinin (60-100%). The results indicate that a 4-5 month exposure of guinea pigs to a biologically relevant level of UVA light produces deleterious effects on the central region of the lenses of the animals. UVA radiation, coupled presumably with the photoreactive UVA chromophore NADPH and trace amounts of O(2) present in the lens nucleus, produced significant levels of oxidized products in the nuclear region over a five month period. The data demonstrate the potentially harmful nature of UVA light with respect to the lens, and highlight the importance of investigating a possible role for this type of radiation in the formation of human cataract.
 ...
PMID:UVA light in vivo reaches the nucleus of the guinea pig lens and produces deleterious, oxidative effects. 1238 92

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

The glass-like transparency of the human eye lens is achieved by the tight packing of abundant crystallin proteins. However, the precise role of the accessory non-crystallin proteins is not well understood. We have carried out 2-DE mapping of these proteins in rat lens. This showed the presence of the high molecular weight filamentous structural proteins spectrin, filensin, tubulin, vimentin, actin and phakinin as well as several forms of potential crystallin oligomers comprised of alphaA, betaB1, betaA1 and betaA4 chains. Other proteins that were present include, heat shock protein 71, WD repeat protein 1, and several enzymes including alpha-enolase, pyruvate kinase, transketolase and aldose reductase. 2-D-DIGE analysis revealed several expression differences between the lens proteomes of male and female rats. Female rat lenses contained lower levels of aldose reductase, increased proteolyic fragments of the structural proteins filensin, vimentin and phakinin and higher levels of potential alphaA, betaB1 and betaA1 crystallin oligomers. Taken together these findings suggest that there are potential differences in oxidative stress regulation between male and female rat lenses, which may have implications on susceptibility to cataract formation. Future studies aimed at elucidating pre-cataractic changes in the non-crystallin proteins described here may facilitate identification of novel markers involved in cataractogenesis.
 ...
PMID:Detection of gender differences in rat lens proteins using 2-D-DIGE. 1634 38

The objective of this investigation was a comparative immunohistochemical study of the crystalline eye lens under normal conditions and in different types of age-associated cataract in man. Control group included the lenses of young men, who died in the accidents and served as lens donors (n = 10, material collected within 1 hr since death). The lens was taken from the patients (age: 60-70 years) during the operation on the occasion of cortical (n = 20) and nuclear (n = 20) cataract. The study has demonstrated phenotype plasticity of lens cells in different types of age-associated cataract. The changes of cell phenotype were shown to depend on cataract type. During the development of cortical age-associated cataract, positive reaction with the monoclonal antibodies against neuron-specific enolase, S-100 protein and vimentin was detected only within the lens cortex. During the formation of nuclear age-associated cataract, positive reaction with the antibodies against alpha-smooth muscle actin, pancytokeratin was found only within the lens nucleus. These data suggest that the differentiated approach to the treatment of different types of age-associated cataract should be worked out.
 ...
PMID:[Immunohistochemical analysis of the lens cells during development of the various types of age-associated cataract in man]. 1819 72

Vimentin is the main intermediate filament (IF) protein of mesenchymal cells and tissues. Unlike other IF-/- mice, vimentin-/- mice provided no evidence of an involvement of vimentin in the development of a specific disease. Therefore, we generated two transgenic mouse lines, one with a (R113C) point mutation in the IF-consensus motif in coil1A and one with the complete deletion of coil 2B of the rod domain. In epidermal keratins and desmin, point mutations in these parts of the alpha-helical rod domain cause keratinopathies and desminopathies, respectively. Here, we demonstrate that substoichiometric amounts of vimentin carrying the R113C point mutation disrupted the endogenous vimentin network in all tissues examined but caused a disease phenotype only in the eye lens, leading to a posterior cataract that was paralleled by the formation of extensive protein aggregates in lens fibre cells. Unexpectedly, central, postmitotic fibres became depleted of aggregates, indicating that they were actively removed. In line with an increase in misfolded proteins, the amounts of Hsp70 and ubiquitylated vimentin were increased, and proteasome activity was raised. We demonstrate here for the first time that the expression of mutated vimentin induces a protein-stress response that contributes to disease pathology in mice, and hypothesise that vimentin mutations cause cataracts in humans.
 ...
PMID:A dominant vimentin mutant upregulates Hsp70 and the activity of the ubiquitin-proteasome system, and causes posterior cataracts in transgenic mice. 1894 Sep 12

The aim of the present work was to perform a comparative immunohistochemical study of the ocular lens in normal conditions and after formation of various type of age-related cataract in humans. The control group consisted of lenses from young men dying from accidents and serving as corneal donors (n = 10, not more than one hour after death). Lenses from patients (aged 60-70 years) undergoing surgery for cortical (n = 20) and nuclear (n = 20) cataracts were studied. The investigations demonstrated plasticity in the phenotype of lens cells in age-related cataract. Changes in the phenotype of lens cells were found to depend on the type of age-related cataract. Development of the cortical variant of age-related cataract was associated with positive reactions with monoclonal antibodies to neuron-specific enolase, S-100 protein, and vimentin only within the lens cortex. Formation of age-related nuclear cataract was associated with positive reactions with antibodies to alpha-smooth muscle actin and pancytokeratin, which were detected only in the lens nucleus. This provides evidence of the need to develop a differential approach to the treatment of different types of age-related cataract.
 ...
PMID:Immunohistochemical analysis of lens cells on formation of different types of age-related cataract in humans. 1897 14

Cataracts are characterized by an opacification of the eye lens, often caused by protein misfolding and aggregation. The intermediate filament protein vimentin, which is highly expressed in lens fiber cells and in mesenchymal tissues, is a main structural determinant in these cells forming a membrane-connected cytoskeleton. Additional functions of vimentin remain to be identified. Here, we demonstrate that a mutation in VIM causes a dominant, pulverulent cataract. We sequenced the complete human VIM gene in 90 individuals suffering from congenital cataract and found a G596A change in exon 1 in a single individual, causing the missense mutation E151K in coil 1B of vimentin. The mutant vimentin formed an aberrant vimentin cytoskeleton and increased the proteasome activity in transfected cells. Furthermore, this mutation causes a severe kinetic defect in vimentin assembly both in vitro and in vivo. Hence, in conjunction with available mouse and cell culture models, our results reveal for the first time an important functional role for vimentin in the maintenance of lens integrity. Finally, this invites novel therapy approaches for cataracts.
 ...
PMID:Dominant cataract formation in association with a vimentin assembly disrupting mutation. 1912 78

A case of adenoma of the non-pigmented ciliary epithelium with smooth muscle differentiation is reported. This uncommon ocular tumor affected a 36-year-old woman, and had caused decreased visual acuity and a total cataract. Ultrasound biomicroscopy disclosed an associated persistent hyperplasic primary vitreous (PHPV). Sectoral cyclectomy with removal of the mass and intracapsular cataract extraction were performed. The tumor was diffusely positive for vimentin, smooth muscle actin, NSE, and S-100, focally for CD68 and Melan-A, and was negative for desmin, EMA, HMB-45, and CD99. Occasional cells reacted for cytokeratin. The proliferation index, as assessed by Ki-67, was below 10%. The overlying non-neoplastic ciliary epithelium was positive for vimentin, NSE, and S-100. Myofilaments are not totally unexpected in ciliary adenomas; however, such a diffuse and strong positivity for smooth muscle actin, as in the present case, has only been observed in one case before, but should be considered in the differential diagnosis of these neoplasms.
 ...
PMID:Adenoma of the non-pigmented ciliary epithelium: a rare intraocular tumor with unusual immunohistochemical findings. 1934 82

Intraocular neoplasms are described in 2 adult rabbits. The left globe of an 8-year-old male rabbit was enucleated after chronic inflammatory disease resulted in a nonvisual eye. The left globe of a 5-year-old female rabbit also was enucleated after a history of lens-induced uveitis, cataract formation, and resultant glaucoma. In both rabbits, histopathology revealed a variably pleomorphic, poorly differentiated, invasive, intraocular spindle cell neoplasm closely associated with lens and lens capsular fragments. Gram stains failed to detect bacterial organisms or Encephalitozoon cuniculi. Polymerase chain reaction assays, used to amplify the 16S RNA gene of numerous bacteria and E. cuniculi, were also negative. Immunohistochemical staining demonstrated strong, diffuse expression for vimentin; however, staining for smooth muscle actin, cytokeratin, S100, and desmin were negative. Long-standing intraocular inflammation and/or traumatic insults to the eyes were considered as causes of these neoplasms. The histologic features of these intraocular neoplasms closely resemble post-traumatic ocular sarcomas in cats.
 ...
PMID:Intraocular sarcomas in two rabbits. 1956 9


<< Previous 1 2 3 4 5 Next >>