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)

A 30-year-old woman was found to have hyperferritinaemia after presenting with menorrhagia and lethargy. Serum iron studies did not confirm iron overload. Further investigations revealed two distinct genetic mutations of iron haemostasis--homozygosity for C282Y mutation of the HFE gene on chromosome 6 and heterozygosity for A40G mutation in the iron response element of ferritin light chain on chromosome 19. These mutations are responsible for the diseases hereditary haemochromatosis (autosomal recessive) and hereditary hyperferritinaemia-cataract syndrome (autosomal dominant) respectively. This is the first description of such a patient.
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PMID:Dual diagnoses of hereditary hyperferritinaemia-cataract syndrome and hereditary haemochromatosis. 1699 31

Hereditary hyperferritinemia cataract syndrome (HHCS) is characterized by distinctive cataracts and high serum ferritin in the absence of iron overload. It is caused by mutations in the iron response element (IRE) of the Ferritin Light Chain (FTL) gene. Here we investigate the genetics of HHCS in a three generation Australian kindred with typical HHCS ocular lens morphology and high ferritin levels. Initial sequencing of the IRE failed to detect any mutations. Sequencing of the entire gene including the promoter region revealed a novel 25 bp deletion upstream of the IRE abolishing the transcription start site. In lymphoblastoid cells, the deletion allele was transcribed from an alternate start site within the lower stem of the IRE and mutation carriers had high cellular L-ferritin levels. This novel deletion in the promoter encompassing the transcription start site of the FTL gene is responsible for HHCS in this kindred. The initial primers for amplifying the IRE similar to those used by other researchers failed to detect this mutation. Therefore the genomic region assessed in HHCS cases for diagnosis should be expanded to include mutations of this type.
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PMID:A novel deletion in the FTL gene causes hereditary hyperferritinemia cataract syndrome (HHCS) by alteration of the transcription start site. 1757 62

Ferritin is a symmetric, 24-subunit iron-storage complex assembled of H and L chains. It is found in bacteria, plants, and animals and in two classes of mutations in the human L-chain gene, resulting in hereditary hyperferritinemia cataract syndrome or in neuroferritinopathy. Here, we examined systemic and cellular ferritin regulation and trafficking in the model organism Drosophila melanogaster. We showed that ferritin H and L transcripts are coexpressed during embryogenesis and that both subunits are essential for embryonic development. Ferritin overexpression impaired the survival of iron-deprived flies. In vivo expression of GFP-tagged holoferritin confirmed that iron-loaded ferritin molecules traffic through the Golgi organelle and are secreted into hemolymph. A constant ratio of ferritin H and L subunits, secured via tight post-transcriptional regulation, is characteristic of the secreted ferritin in flies. Differential cellular expression, conserved post-transcriptional regulation via the iron regulatory element, and distinct subcellular localization of the ferritin subunits prior to the assembly of holoferritin are all important steps mediating iron homeostasis. Our study revealed both conserved features and insect-specific adaptations of ferritin nanocages and provides novel imaging possibilities for their in vivo characterization.
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PMID:Homeostatic mechanisms for iron storage revealed by genetic manipulations and live imaging of Drosophila ferritin. 1760 97

Iron, an essential element for many important cellular functions in all living organisms, can catalyze the formation of potentially toxic free radicals. Excessive iron is sequestered by ferritin in a nontoxic and readily available form in a cell. Ferritin is composed of 24 subunits of different proportions of two functionally distinct subunits: ferritin H and L. The expression of ferritin is under delicate control and is regulated at both the transcriptional and post-transcriptional levels by iron, cytokines, hormones, and oxidative stress. Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections, and malignancies. While elevated levels of ferritin are characteristic of adult-onset Still's disease and hemophagocytic syndrome, both associated with inflammation, it has scantly been evaluated in other autoimmune diseases. In this review, we describe ferritin structure and function, hyperferritinemia in disease states and in autoimmune diseases.
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PMID:Ferritin in autoimmune diseases. 1764 33

This report describes a family with hereditary hyperferritinemia cataract syndrome. Inheritance is autosomal dominant and clinical characteristics of this syndrome are familial cataracts of early development and elevated serum ferritin levels but otherwise normal iron studies and haematological parameters. It is important to increase awareness of this entity in order to diagnose new cases and avoid unnecessary diagnostic tests and inadequate treatments.
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PMID:[Hereditary syndrome of hyperferritinemia and cataract]. 1789 22

Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels buildup with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich's ataxia, and panthothenate kinase-associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age-matched controls. Over the past 10 years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter-1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron-regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including glaucoma, cataract, AMD, and conditions causing intraocular hemorrhage. While iron deficiency must be prevented, the therapeutic potential of limiting iron-induced ocular oxidative damage is high. Systemic, local, or topical iron chelation with an expanding repertoire of drugs has clinical potential.
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PMID:Iron homeostasis and toxicity in retinal degeneration. 1792 Oct 41

The definition of oxidative stress implies increased oxidant production in animal cells characterized by the release of free radicals, resulting in cellular degeneration. The imbalance between excess free radical production and the antioxidant defense causes cellular damage resulting in lipid peroxidation. Oxidative stress is involved in many ocular diseases such as age-related macular degeneration, retinopathy of prematurity, retinal light damage, and cataract. Reactive oxygen species are involved in this process. The pathogenesis of age-related macular degeneration is largely unknown. Excessive light and iron may enhance the progression of this disease. In in vitro study of the ciliary body, gamma irradiation inhibits TPR53BP2 expression associated with apoptotic cell death, and increased BCL2 is evident just after gamma irradiation. Exposure to ultraviolet light has been postulated as a cause of age-related macular degeneration (AMD), perhaps through damage to the retinal pigment epithelium. It seems logical, therefore, to replace the aging, yellowing lens with a blue light-absorbing yellow intraocular lens (IOL) in cataract surgery. The issue of whether cataract surgery is a risk factor for the development or progression of AMD remains controversial. In vivo studies suggest that lipid peroxidation decreases in the vitreous and retina after cataract surgery with or without intraocular lens implantation.
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PMID:[Oxidative stress in ocular disease]. 1824 Jun

Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA structures, signaling pathways and protein catalysts. Ferritin synthesis is regulated by cytokines (tumor necrosis factor-alpha and interleukin-1alpha) at various levels (transcriptional, post-transcriptional, translational) during development, cellular differentiation, proliferation and inflammation. The cellular response by cytokines to infection stimulates the expression of ferritin genes. The immunological actions of ferritin include binding to T lymphocytes, suppression of the delayed-type hypersensitivity, suppression of antibody production by B lymphocytes, and decreased phagocytosis of granulocytes. Thyroid hormone, insulin and insulin growth factor-1 are involved in the regulation of ferritin at the mRNA level. Ferritin and iron homeostasis are implicated in the pathogenesis of many disorders, including diseases involved in iron acquisition, transport and storage (primary hemochromatosis) as well as in atherosclerosis, Parkinson's disease, Alzheimer disease, and restless leg syndrome. Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections and malignancies, and in systemic lupus erythematosus correlates with disease activity. Some evidence points to the importance of hyperferritinemia in dermatomyositis and multiple sclerosis, but further mechanistic investigations are warranted.
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PMID:Hyperferritinemia in autoimmunity. 1830 May 83

The level of serum ferritin normally parallels the concentration of storage iron within the body. In the absence of chronic diseases elevated serum ferritin levels will lead to the diagnosis congenital haemochromatosis. However, there are genetic disorders with high ferritin levels without any sign of iron overload. A case history of a patient suffering from cataract at young age and high ferritin levels is described. Because his mother and his three sons also had cataract at young age and high ferritin levels the diagnosis hereditary hyperferritinaemia-cataract syndrome (HHCS) was made. The diagnosis was confirmed by detection of one of the mutations responsible for the syndrome.
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PMID:Hyperferritinaemia not always a sign of iron overload. 1833 93

Quercetin is a dietary bioflavonoid which has been shown to inhibit lens opacification in a number of models of cataract. The objectives of this study were to determine gene expression changes in human lens epithelial cells in response to quercetin and to investigate in detail the mechanisms underlying the responses. FHL-124 cells were treated with quercetin (10 microM) and changes in gene expression were measured by microarray. It was found that 65% of the genes with increased expression were regulated by the hypoxia-inducible factor-1 (HIF-1) pathway. Quercetin (10 and 30 microM) induced a time-dependent increase in HIF-1alpha protein levels. Quercetin (30 microM) was also responsible for a rapid and long-lasting translocation of HIF-1alpha from the cytoplasm to the nucleus. Activation of HIF-1 signaling by quercetin was confirmed by qRT-PCR which showed upregulation of the HIF-1 regulated genes EPO, VEGF, PGK1 and BNIP3. Analysis of medium taken from FHL-124 cells showed a sustained dose-dependent increase in VEGF secretion following quercetin treatment. The quercetin-induced increase and nuclear translocation of HIF-1alpha was reversed by addition of excess iron (100 microM). These results demonstrate that quercetin activates the HIF-1 signaling pathway in human lens epithelial cells.
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PMID:Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. 1972 6


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