Disease relevance of Keratoconus

• Epikeratoplasty. The surgical correction of aphakia, myopia, and keratoconus [1].
• Severe loss of vision was the indication for surgery in each case, and was associated with aggressive and repeated incisional refractive attempts to correct astigmatism, hyperopic overcorrection, residual myopia, or refractive errors associated with keratoconus [2].
• The lens has been used primarily with aphakic children, but it has also been tolerated by children with anisometropia, high myopia, and keratoconus [3].
• The yield of such studies may be high for an understanding of such diseases as myopia, retinal detachment, and keratoconus [4].
• In a series of 64 patients with deep corneal opacities (14 with Descemet's tears, 8 with posterior polymorphous dystrophy, 12 with interstitial keratitis, and 30 with keratoconus), specular microscopy enabled the differentiation of deep corneal changes provided some degree of corneal clarity was retained [5].

High impact information on Keratoconus

• Molecular basis for keratoconus: lack of TrkA expression and its transcriptional repression by Sp3 [6].
• We suggest that an imbalance in Sp transcription-factor isoforms may play a role in controlling the NGF signaling, thus contributing to the pathogenesis of keratoconus [6].
• Keratoconus is the most common corneal dystrophy that leads to severe visual impairment [6].
• A VSX1 HD mutation, R166W, that impairs DNA binding and causes keratoconus in humans, hindered repressor function [7].
• This information may help elucidate the molecular pathways leading to the altered alpha1-proteinase inhibitor expression in keratoconus [8].

Chemical compound and disease context of Keratoconus

• However, the macromolecules contained an unsulfated glycoconjugate that was nearly as large as the normal keratan sulfate chains isolated from the keratoconus keratan sulfate-proteoglycan and contained the same relative proportions of labeled glucosamine, mannose, and fucose [9].
• Characterization of the immunoprecipitates showed that macular corneas did not make keratan sulfate proteoglycan but did synthesize an immunoreactive glycoprotein in nearly equal amounts as keratan sulfate proteoglycan was synthesized by the keratoconus cornea [9].
• Androgen-dependent hereditary mouse keratoconus: linkage to an MHC region [10].
• There was no indication of decreased hydroxylysine levels in keratoconus, and there were no clinical indications of a generalized connective tissue disorder [11].
• Organ cell cultures of normal and keratoconus corneal specimens were labeled with radioactive proline and analyzed by CM-cellulose chromatography and slab gel electrophoresis to determine collagen biosynthesis [12].

Biological context of Keratoconus

• In the cornea-thinning disease keratoconus, down-regulation of the alpha1-proteinase inhibitor gene and increased Sp1 expression have both been demonstrated [8].
• Gene expression profile studies of human keratoconus cornea for NEIBank: a novel cornea-expressed gene and the absence of transcripts for aquaporin 5 [13].
• CONCLUSIONS: Mutational analysis of the VSX1 gene in a series of Italian patients revealed one novel mutation and confirmed an important role played by this gene in a significant proportion of patients affected by keratoconus, when it is inherited as an autosomal dominant trait with variable expressivity and incomplete penetrance [14].
• RESULTS: The locus for keratoconus with cataract was mapped to a 6.5-Mb region of the long arm of chromosome 15, at 22.33-24.2 between CYP11A and D15S211 [15].
• Although one cannot conclude inheritance patterns based on this limited evaluation, the findings in this family support previous observations that keratoconus can be familial, and that Fuchs' corneal dystrophy has a female predilection with an autosomal-dominant inheritance pattern [16].

Anatomical context of Keratoconus

• Compared with normal and other diseased controls, the labeling was enhanced for cathepsin G but was diminished for alpha 1-PI in the epithelium of keratoconus corneas [17].
• The present study explored the possible involvement in keratoconus of Krüppel-like factor 6 (KLF6), a transcription factor previously described to be essential for the integrity of the corneal epithelium [18].
• Using a second method with biotin-labeled lectins as probes, we confirmed that increased amounts of glycoconjugates would bind to concanavalin A and R communis agglutinin I in stromal cells of patients with keratoconus compared with those of the control subjects [19].
• This study suggests that plasma membranes of cells derived from some patients with keratoconus may contain elevated amounts of glycoconjugates with glucose and/or mannose, terminal galactose, and N-acetylgalactosamine residues [19].
• In keratoconus, MMP-1 expression was slightly augmented in epithelial cells and also appeared locally in a scattered manner in the stroma [20].

Gene context of Keratoconus

• Increased gelatinolytic activity in keratoconus keratocyte cultures. A correlation to an altered matrix metalloproteinase-2/tissue inhibitor of metalloproteinase ratio [21].
• Stromal scars of keratoconus corneas also had increased staining with TIMP-1 and TIMP-2 antibodies [22].
• CONCLUSION: These data suggest that TIMP-1 and TIMP-2 are important for scar formation and corneal remodeling, since they were found in increased amounts at radial keratotomy incision sites and keratoconus scars [22].
• The significance of the focal stromal defects in TIMP-3 staining, associated with absence of Bowman's layer on keratoconus corneas, needs to be elucidated [22].
• We suggest the unambiguously expressed DSG3 protein to be used as a marker for keratoconus [23].

Analytical, diagnostic and therapeutic context of Keratoconus

• The macromolecules in macular corneas and in keratoconus corneas, an abnormality not involving proteoglycans, were biosynthetically labeled with [3H]mannose and [14C]glucosamine in organ culture, and the keratan sulfate proteoglycans were immunoprecipitated with antibodies against the protein core of monkey keratan sulfate proteoglycan [9].
• Enzymatic assays and western blot analysis were carried out for cathepsins B and G. In addition, an in situ zymography procedure was used to examine the gelatin- and casein-digesting activities in corneas with keratoconus [24].
• Chromatin immunoprecipitation (ChIP) assays were performed to confirm the interactions between KLF6 and promoters of the genes affected in keratoconus [18].
• This study supports the hypothesis that the degree of post-penetrating keratoplasty myopia in patients with keratoconus can be decreased by reducing recipient-donor trephine disparity [25].
• In the clinical evaluation, 11 patients with keratoconus (8 men, 3 women; 25.1 +/- 4.9 years of age) who could not wear hard contact lenses due to constant pain or inadequate lens fitting were given oxygen-permeable piggyback contact lenses and were observed for at least 9 months [26].

References