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)

Sensitive high-performance liquid chromatography methods were employed to assess regional distribution of adenine, guanosine and uridine nucleotides in clear and cataractous human eye lenses. According to slit-lamp examination, three forms of senile cataract were distinguished: (1) supranuclear or deep cortical cataract (typical senile cataract), (2) primary nuclear cataract (cataracta brunescens) and (3) subcapsular cortical cataract associated either with a supranuclear (3a) or a secondary nuclear cataract (3b). Except for AMP, which was highest in the nuclear fraction, all other nucleotides (ATP, ADP, GTP, and UTP) were predominantly located in the anterior cortex (plus epithelium) of clear as well as cataractous lenses, that is, ATP levels in the nucleus amounted to 20% of those found in the anterior cortex (plus epithelium); ATP levels in the posterior cortex were about 60% of those in the anterior cortex (plus epithelium). Significant differences in the absolute regional nucleotide level existed between the different forms of cataract. Highest ATP levels were found in the anterior cortex (plus epithelium) of clear lenses and deep or supranuclear cortical cataract. The ATP level was slightly diminished in primary nuclear cataract and in supranuclear cortical cataract when associated with an early subcapsular cortical cataract. ATP levels were depressed to less than 30% in the anterior cortex (plus epithelium) of lenses with a subcapsular cortical cataract when associated with either an early secondary nuclear or a mature cataract. Furthermore, the ATP/ADP ratio was decreased in this form of senile cataract. The decrease in lens nucleotide level did not correlate with increased age. These data suggest that decreases in regional ATP level are a secondary event and do not appear to be causally involved in the genesis of the 'cataracta senilis'.
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PMID:Nucleotide levels in human lens: regional distribution in different forms of senile cataract. 292 Jul 83

Statins are commonly prescribed cholesterol-lowering agents which inhibit the rate-limiting enzyme of the cholesterol biosynthetic pathway. In addition to inhibiting cholesterol synthesis, statins also inhibit the synthesis of other sterol and non-sterol compounds produced by the pathway including the isoprenoids, farnesyl (FP) and geranylgeranyl pyrophosphate (GGP). Certain proteins, most notably small GTP-binding proteins of the Ras superfamily, must be post-translationally modified by addition of a farnesyl or geranylgeranyl moiety in order to be properly targeted to membranes and to be active. Statins have been shown to affect cellular processes such as proliferation, signaling and apoptosis and it is likely that these effects are due, at least in part, to decreased isoprenoid synthesis. Certain statins have been shown to produce cataracts in experimental animals. We have previously demonstrated that lenses exposed to lovastatin during organ culture may develop cataracts as well, and we proposed that this resulted from decreased prenylation of small GTP-binding proteins. To test our hypothesis, rat lenses were exposed to lovastatin in organ culture with concomitant supplementation of the medium with GGP and/or FP. The results clearly demonstrated that GGP strongly inhibited lovastatin-induced lens opacification in this system while FP had little effect. GGP also markedly reduced the histological changes and the increased epithelial cell apoptosis induced in the cultured lenses by lovastatin. The data indicate that inhibition of protein prenylation, perhaps of Rho GTPases, is an important factor in the lovastatin-induced cataract in vitro.
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PMID:Geranylgeranyl pyrophosphate counteracts the cataractogenic effect of lovastatin on cultured rat lenses. 1245 72

Rupture of lens cataract (RLC) in the mouse is a spontaneous mutation inherited by a single autosomal recessive gene mapped on chromosome 14. Fine mapping of the mutant locus revealed a nucleotide deletion of 27-bp at the end of 15th exon of Dock5 (Dedicator of cytokinesis-5), a member of the Dock gene superfamily. Since the deletion occurred in-frame, the RLC-DOCK5 protein had a deletion of 9 amino acids (a.a. 506-514) in the DHR1 (DOCK homology region-1) domain that is essential for DOCK5, a GTP-exchanger for Rac1. Although Dock5 mRNA was intensely expressed equally in mutant and wild-type lenses, DOCK5 protein was hardly detectable in the mutant lens. In contrast, expression of Dock180, another member of Dock subfamily A, was not affected in RLC. Immunohistochemically, DOCK5 was stained intensely in the cytoplasm of the anterior epithelial cells and weakly in lens fiber of the wild type lenses, but little in RLC lens. These observations suggest that the mutation may somehow destabilize DOCK5 protein. We propose to designate the mutant allele of rlc as Dock5rlc. Relevance of the signaling pathway involving DOCK5-RAC1 in maintenance of lens integrity of growing lens is discussed.
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PMID:Mutation of Dock5, a member of the guanine exchange factor Dock180 superfamily, in the rupture of lens cataract mouse. 1839 77