Disease relevance of Cataract

• Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy [1].
• We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sjögren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy [2].
• Thus, our results suggest that mutations in MYH9 result in three megakaryocyte/platelet/leukocyte syndromes and are important in the pathogenesis of sensorineural deafness, cataracts and nephritis [3].
• Additionally, CDPX2 patients may have asymmetric rhizomesomelia, sectorial cataracts, patchy alopecia, ichthyosis and atrophoderma [4].
• Rothmund-Thomson syndrome (RTS; also known as poikiloderma congenitale) is a rare, autosomal recessive genetic disorder characterized by abnormalities in skin and skeleton, juvenile cataracts, premature ageing and a predisposition to neoplasia [5].

Psychiatry related information on Cataract

• The oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, mental retardation, and renal Fanconi syndrome [6].
• Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis [7].
• Here we report the presence of significantly increased cataracts in the lenses of an Abeta-transgenic mouse model for Alzheimer disease and their amelioration upon treatment with EUK-189, a synthetic SOD/catalase mimetic [8].
• In a multivariable analysis, lower income, confidence in the effectiveness of tamoxifen, and concern about fractures were associated with being inclined to take it; concern about pulmonary embolism, dyspareunia, cataracts, and low self-perceived breast cancer risk were associated negatively with taking tamoxifen [9].

High impact information on Cataract

• Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome [10].
• As ocular cataracts are a characteristic feature of DM, these results demonstrate that decreased SIX5 transcription is important in the aetiology of DM [11].
• Missense mutations in MIP underlie autosomal dominant 'polymorphic' and lamellar cataracts linked to 12q [12].
• MHA and SBS can be differentiated by subtle ultrastructural leukocyte inclusion features, whereas FTNS is distinguished by the additional Alport-like clinical features of sensorineural deafness, cataracts and nephritis [3].
• A 17-bp insertion in the 3'-end of the coding sequence, resulting in a frame shift, occurred in a patient with ASMD and cataracts, and a G-->A substitution, changing a codon for serine into a codon for asparagine, in the 5'-end of the gene occurred in a patient with congenital cataracts [13].

Chemical compound and disease context of Cataract

• Galactokinase is an essential enzyme for the metabolism of galactose and its deficiency causes congenital cataracts during infancy and presenile cataracts in the adult population [14].
• Higher cumulative lifetime doses of beclomethasone were associated with higher risks of posterior subcapsular cataracts (P for trend <0.001); the highest prevalence (27 percent) was found in subjects whose lifetime dose was over 2000 mg (relative prevalence, 5.5) [15].
• Near-total glutathione depletion and age-specific cataracts induced by buthionine sulfoximine in mice [16].
• Ah locus: genetic differences in susceptibility to cataracts induced by acetaminophen [17].
• Inhibitors of cholesterol synthesis and cataracts [18].

Biological context of Cataract

• Myotonic dystrophy, or dystrophia myotonica (DM), is a highly variable multisystem disease in which the classic adult-onset form displays progressive muscle wasting, cataracts, heart block, gonadal atrophy, insulin resistance and neuropsychiatric impairment [19].
• The cataracts seen in Ofl heterozygotes and human MAF mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract [20].
• Huntingtin Interacting Protein 1 mutations lead to abnormal hematopoiesis, spinal defects and cataracts [21].
• Dominantly inherited cataracts with differing clinical features were found in two families carrying different point mutations in the gene encoding lens water channel protein AQP0 (major intrinsic protein, MIP) [22].
• The present studies were undertaken to determine whether sorbinil, a chemical inhibitor of aldose reductase that has been shown to prevent and reverse diabetic cataracts and neuropathy, also could prevent the vascular permeability and collagen cross-linking changes in this model [23].

Anatomical context of Cataract

• On consideration of the proposed function of BFSP2 in the lens cytoskeleton, it is likely that this alteration is the cause of cataracts in the members of the family we studied [24].
• This is the first documented report of an inborn error of P5CS and suggests that this disorder should be considered in the differential diagnosis in patients with neurodegeneration and/or cataracts and connective tissue disease [25].
• Bru heterozygous mice display defects similar to Axenfeld-Rieger anomaly, including iris defects, corneal opacity, vacuolar cataracts, significant iris/corneal adhesions, buphthalmos and optic nerve cupping, a sign indicative of glaucoma [26].
• The frequency of diabetic cataracts was reduced by statil, and erythrocyte and kidney sorbitol levels were normalized, confirming the efficacy of ARI [27].
• The results of this x-ray diffraction study provide evidence for fundamental changes in the lens fiber cell plasma membrane structure in cataracts, including the presence of more prominent and highly ordered, immiscible cholesterol domains [28].

Gene context of Cataract

• A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD [13].
• Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts [11].
• Moreover, these observations predict that less severe defects in the AQP0 protein may contribute to lens opacity in patients with common, less fulminant forms of cataracts [22].
• Targeted null mutations in Gja8 and Gja3 in mice cause cataracts with recessive inheritance [29].
• Three of four transgenic families expressing the truncated FGF receptor exhibited lens defects ranging from cataracts to severe microphthalmia [30].

Analytical, diagnostic and therapeutic context of Cataract

• These channels were blocked by tamoxifen and, in organ culture, tamoxifen led to lens opacity associated with cataracts at clinically relevant concentrations [31].
• The variation of the phase-separation temperature (Tc) was studied in lenses during formation of cataracts induced by a subcutaneous injection of sodium selenite [32].
• The measurements used were urinary concentration of galactose during pregnancy in adults and in infants from the newborn period through the first 5 months of life; the rate of elimination of an intravenous infusion of galactose; and slit-lamp examination of the lens for evidence of cataracts [33].
• These data, together with data from earlier experimental and epidemiologic studies, suggest that long-term consumption of vitamin C supplements may substantially reduce the development of age-related lens opacities [34].
• However, liver function tests and eye examinations for possible lens opacities are advised, and further long term studies in larger groups of patients are necessary before the side effect profile of lovastatin will be clearly established [35].

References