Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keratoconus is an ocular condition that causes corneal thinning, cone formation and scarring. In view of a hypothesis that activated MMP-2 may initiate or facilitate disease progression, the MMP-2/TIMP systems of stromal cells derived from normal and keratoconic corneas have been compared. To achieve this, stromal cell cultures were established from normal, clear keratoconic (KCS-1) and scarred keratoconic (KCS-2) corneas. The secreted MMP-2 was assayed using [(3)H]Type IV collagen and analysed by zymography. Optimally maintained and nutrient deprived cells were subsequently incubated with [(3)H]lysine. The secreted radiolabelled macromolecules were separated and quantified. The results obtained indicated that optimally maintained KCS-1 stromal cells produced more MMP-2 than normal stromal cells but not TIMP. Nutrient deprivation induced MMP-2 activation and cell death. Surviving cells upregulated TIMP-1 synthesis and in this respect became similar to the KCS-2 stromal cells that did not excessively generate activated MMP-2 or die as a consequence of nutrient deprivation. From these results, it was concluded that KCS-1 stromal cells over-expressed MMP-2 without increasing TIMP production. This may facilitate MMP-2 activation in vivo and hence advance the keratoconic condition. KCS-2 cultures over-expressed both MMP-2 and TIMP-1. Because TIMP-1 inhibits MMP-2 activity and protects against cell death it may be of significance in initiating repair processes and curtailing keratoconus.
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PMID:Keratoconus: matrix metalloproteinase-2 activation and TIMP modulation. 1651 44

Keratoconus is a bilateral, non-inflammatory and progredient corneal ectasia with an incidence of approximately 1 per 2,000 in the general population. Within the second decade of life the cornea develops a conical shape, due to thinning of the corneal stroma with subsequent irregular astigmatism and myopia leading to marked impairment of vision. The most common presentation of the keratoconus is as a sporadic disorder, but it has long been recognized that a significant minority of patients exhibit a family history as an autosomal dominant mode of inheritance. Most investigators suggest complete penetrance of predisposing factors with variable phenotypic expression. In some patients heterozygous mutations in the VSX1 gene are described as the underlying gene defect. An association with Down syndrome, monosomia X (Turner syndrome), Leber's congenital amaurosis, mitral valve prolaps, collagenosis, retinitis pigmentosa and Marfan syndrome is described. The role of corneal cells in the pathogenesis of keratoconus is supported by the published reports of recurrence of keratoconus in eyes after penetrating keratoplasty due to graft repopulation by the recipient cells. Placido-based computeed videokeratographic corneal curvature mapping systems, linked with pachymetry, are useful for identifying overt and subclinical cases of keratoconus. Different indices may quantify the clinical features of keratoconus and may improve the classification. We compared videokeratometric data (Fourier series harmonic analysis and wavefront analysis) in eyes with keratoconus to answer the question of which parameters are useful for early diagnosis of keratoconus.
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PMID:[Keratoconus: epidemiology, risk factors and diagnosis]. 1680 19

Pellucid marginal corneal degeneration (PMCD) is an ectatic corneal disorder characterized by a peripheral, noninflammatory band of thinning of the inferior cornea. This condition often is misdiagnosed with keratoconus, with which it shares several clinical, videotopographic, and histologic aspects. Furthermore, as with keratoconus, hydrops and spontaneous corneal perforation can occur. We report the case of a 56-year-old man with confirmed PMCD, emphasizing the diagnostic approach, the disease follow-up, and its complication in spontaneous acute corneal hydrops. Finally, regarding this case, authors collect the clinical and videotopographic characteristics of PMCD and discuss the different therapeutic options.
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PMID:[Acute spontaneous corneal hydrops in a patient with pellucid marginal corneal degeneration]. 1688 86

In keratoconus, the cornea becomes progressively ectactic resulting in severe visual impairment. Here, we use a combination of videokeratography and synchrotron X-ray diffraction to investigate the relationship between corneal shape and thickness, and the distribution and predominant orientation of stromal fibrillar collagen in five keratoconus corneas. In all but the least advanced case, the thinning and ectasia measured in vivo using corneal videokeratography was accompanied by corresponding changes in the relative distribution and orientation of stromal collagen in the excised corneal buttons. Although the most severe case of keratoconus possessed the most pronounced stromal collagen alterations, and only a minor disruption to stromal collagen arrangement was seen in the least advanced case, a variability in the extent of stromal collagen alteration was seen between these clinical extremes. The observed abnormalities in collagen distribution and orientation are consistent with a mechanism of keratoconus progression that involves inter-fibrillar or inter-lamellar slippage causing a redistribution of tissue within the cornea.
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PMID:A study of corneal thickness, shape and collagen organisation in keratoconus using videokeratography and X-ray scattering techniques. 1717 18

The aim of cross-linking therapy is to prevent keratoconus progression and stabilize the present refractive situation. A 41-year-old man was treated with collagen cross-linking in one eye. Postoperatively there were a diffuse subepithelial opacification and a paracentral corneal thinning. This superficial scarring in the sense of a "haze" disappeared only gradually despite intensive therapy.
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PMID:[Hazeformation (corneal scarring) after cross-linking therapy in keratoconus]. 1766 Oct 57

Ultraviolet radiation (UVR) is a risk factor for the development of ocular disease in humans, including acute photokeratitis, chronic corneal spheroidal degeneration, and cataract formation. This report describes the ocular lesions seen in 21 mice chronically exposed to UVR as part of a skin carcinogenicity study. All globes were affected to varying degrees. The primary lesion, not previously reported in UVR-exposed mice, was marked loss of keratocytes relative to age-matched controls. Secondary lesions included corneal stromal thinning, keratoconus, corneal vascularization and fibrosis, keratitis, globe rupture, and phthisis bulbi. In addition, more than 90% of UVR-exposed and unexposed lenses had evidence of cataract formation; this is the first report of the occurrence of spontaneous cataracts in 129 mice. In a subsequent study, apoptotic cells were identified histologically and by cleaved caspase 3 immunoreactivity in the corneal epithelium and, less commonly, in the corneal stroma after acute UVR exposure. Based on this finding, we propose that the loss of keratocytes observed in the chronic study was due to UVR-induced apoptosis.
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PMID:Ultraviolet radiation-induced corneal degeneration in 129 mice. 1794 56

The application of aberrometry in the field of refractive surgery has led to the availability of several methods of measuring ocular aberrations in a clinical setting. A case series from four patients diagnosed with corneal thinning disorders is described in this paper (keratectasia following refractive surgery, pellucid marginal degeneration, forme fruste keratoconus or keratoconus). These cases demonstrate how aberrometry can be used to help in the differential diagnosis of patients with corneal thinning disorders, although the standard polynomial fitting for aberrometry data may fail in some patients. Measurement of ocular aberrations can provide an improved description of the optical quality of the eye and hence can be useful to the clinician in evaluating eyes with optical abnormalities.
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PMID:Aberrometry in clinical practice: case series. 1860 58

The success of riboflavin photochemical cross-linking of the cornea in treating keratoconus and post-surgical keratectasia has prompted interest in cross-linking scleral tissue with a potential application to stabilize myopic progression. Applying an UVA light source to the sclera is difficult, particularly in the posterior region. An alternate pharmacologic approach to scleral cross-linking may be possible. The present study was undertaken in order to identify nitrite related compounds capable of inducing scleral tissue cross-linking and to gain information regarding the possible chemical mechanisms involved. 8x4 mm strips of porcine and human sclera were incubated in various concentrations of nitrite related agents (1-100mM) at 37 degrees C. pH 7.4 was used for all experiments except those involving NaNO(2). Following a 24-96 h incubation period, the samples were tested for cross-linking effects using thermal shrinkage temperature (T(s)) analysis. Several compounds were studied including NaNO(2), 2-nitroethanol, 2-nitro-1-propanol, 3-nitro-2-pentanol, 2-nitrophenol, 2-nitroethane, 2-aminoethanol, isopentyl nitrite, DPTA/NO, DETA/NO, and urea, a nitrous acid trap. The results indicate that short chain aliphatic beta-nitro alcohols (2-nitroethanol, 2-nitro-1-propanol, and 3-nitro-2-pentanol) are particularly effective cross-linking agents at pH 7.4, showing both time and concentration dependent effects. Furthermore, nitrosation does not appear to induce tissue cross-linking. In conclusion, aliphatic beta-nitro alcohols can cross-link scleral tissue at physiologic pH and temperature. Since beta-nitro alcohols are known to have reasonable toxicity profiles, these agents could find utility as pharmacologic cross-linking agents for scleral thinning disease.
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PMID:Aliphatic beta-nitro alcohols for non-enzymatic collagen cross-linking of scleral tissue. 1861 42

Keratoconus is a bilateral ectatic disorder characterized by the central thinning of corneal tissue leading to visual impairment. To investigate the possibility of visual system homeobox 1 (VSXI) as a candidate susceptibility gene for Korean patients with keratoconus, we performed a mutation screening of the VSXI gene in 249 unrelated patients with keratoconus and 208 control subjects without the ocular disorder. We found two heterozygous novel missense mutations in exon 2: N151S and G160V. The G160V mutation was identified in 13 keratoconus patients (5.3%), and the N151S mutation was found in only one keratoconus patient (0.4%). We also detected three synonymous polymorphisms and four intragenic polymorphisms. The IVS1-11*a allele was associated with a significantly increased risk of keratoconus in Korean patients [3.6 vs. 0.5%, p = 0.001, odds ratio (OR) = 7.76, 95% confidence interval (CI) 1.989-30.241). Other polymorphisms did not show an association with keratoconus risk. Our data is the first reported VSX1 mutation screening in Korean keratoconus patients. We detected two novel missense mutations and one intragenic polymorphism in the VSX1 gene, which show a strong statistical association with unrelated keratoconus patients. Consequently, our study suggests that VSX1 gene variants seem to be significant genetic variants for keratoconus predisposition in unrelated Korean patients.
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PMID:VSX1 gene variants are associated with keratoconus in unrelated Korean patients. 1862 69

Keratoconus is a debilitating ocular disease characterised by progressive asymmetrical thinning of the cornea, the clear covering at the front of the eye. The resulting protrusion of the cornea results in severe refractive error, in the most severe cases requiring corneal grafting. It is a complex disease with a genetic component. Despite several reports of linked loci, major gene identification has been elusive. A genome-wide linkage scan in a large Australian pedigree with apparent autosomal dominant keratoconus was conducted using the Affymetrix 10K SNP chip and two regions of linkage identified. Functional candidate genes from within both linkage peaks were assessed for corneal expression and screened for mutations in affected family members. Equal evidence of linkage was detected to both 1p36.23-36.21 and 8q13.1-q21.11 with LOD scores of 1.9. Analysis of both loci concurrently suggests digenic linkage with two-locus LOD score of 3.4. All affected individuals carry identical haplotypes at both loci. Carriers of either linked haplotype without the other do not have keratoconus. No mutations were identified in the following candidate genes expressed in the cornea: ENO1, CTNNBIP1, PLOD1, UBIAD1, SPSB1 or TCEB1. Although the pedigree appears to demonstrate simple autosomal dominant inheritance, the disorder is actually genetically complex. This pedigree may provide a link between inherited forms of keratoconus and sporadic cases.
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PMID:Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci. 1879 34


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