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 a noninflammatory corneal disorder characterized by gradual stromal thinning and astigmatism. Altered degradation of corneal extracellular matrix is a suggested etiology for this disorder. In the present study we established keratocyte cultures from normal and keratoconus corneas and investigated the roles that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP, TIMP-2) may play. After chemical modification (reduction and alkylation) to remove the inhibitor and activation of enzyme with p-aminophenylmercuric acetate (APMA), keratoconus-conditioned media displayed a significant increase (p < 0.05) in the total potential gelatinolytic activity when compared with normal culture media treated in a similar manner. Basal levels of gelatinolytic activity in keratoconus culture media (no reduction, alkylation, or APMA treatment), determined by two different assay methods, tended to be about twice that of normal cell cultures. By zymography, both keratoconus and normal cultures showed identical enzyme patterns, which represented MMP-2 (72 kDa) in its proform and, depending on the treatment of the media, varying amounts of activated MMP-2 (65 kDa). This suggests that the increased gelatinolytic activity in keratoconus was not correlated with an increased appearance of either the 65-kDa-activated form of MMP-2 or a new MMP species. In addition, no differences in the amount of MMP-2 were detected that could account for the increased activities in keratoconus cultures. However, a relative decline in the detectable TIMP levels in keratoconus cultures resulted in an apparent three-fold increase in the ratio of MMP-2/TIMP. Northern blots showed no significant changes in mRNA levels for MMP-1, MMP-2, MMP-3, TIMP, or TIMP-2. These data suggest that a possible alteration in the interaction between MMP-2 and TIMP may play a role in the increased gelatinolytic activity seen in keratoconus tissues.
Cornea 1994 Mar
PMID:Increased gelatinolytic activity in keratoconus keratocyte cultures. A correlation to an altered matrix metalloproteinase-2/tissue inhibitor of metalloproteinase ratio. 815 82

Many investigators have measured corneal thickness after keratoplasty using organ culture and storage mediums. Values for corneal thickness were found to stabilize 6-12 months postoperatively, reaching normal values. We followed 59 corneal transplant recipients whose donor tissue was obtained from organ culture (average preservation time 13 days) for > 1 year retrospectively. The overall graft survival was 95.3%. The graft was thick in the early postoperative period. It subsequently became thinner, reaching the lowest level 5-9 months postoperatively (mean 0.48 mm, SD 0.04). After this period the corneas gradually became thicker and reached the normal corneal thickness. The extreme thinning of transplanted corneas in the first postoperative year has not been described before. We found a negative correlation between conservation time and thickness 5-9 months postoperatively. We postulate that organ culture may have a high impact on keratocyte function.
Cornea 1993 Jul
PMID:Extreme temporary thinning after keratoplasty of organ-cultured corneas. 784 17

Human type IV collagen discs were found to support proliferation and adhesion of rabbit corneal epithelial cells in tissue culture. To assess the biocompatibility of this synthetic collagen for epikeratoplasty, seven eyes of seven rhesus monkeys underwent epikeratoplasty with lenticules made of human type IV collagen. Eye rubbing by the animals expulsed two of the lenticules and caused failure of two to epithelialize completely. The remaining three lenticules epithelialized, remained clear, and caused no adverse effects on the eye. Two of these lenticules developed focal areas of subepithelial thinning 3 months postoperatively and the third lenticule has remained stable for 30 months. The presence of epithelial attachment components at the epithelial-lenticule interface was demonstrated by immunolocalization. Histopathologic and ultrastructural examination revealed focal areas of epithelial invasion and degradation of the lenticule. Neutral proteases were detected in the thinning region of one specimen. Human type IV collagen supports epithelialization in vivo and may have potential as a biomaterial for epikeratoplasty, but the stability of the material must be improved.
Cornea 1993 Jan
PMID:Synthetic epikeratoplasty in rhesus monkeys with human type IV collagen. 845 30

Eleven patients with blue sclera, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents were examined between January 1983 and September 1991. The clinical diagnosis was consistent with the Ehlers-Danlos syndrome type VI phenotype in all patients. A "halo" sign at the limbus was present in all patients. Corneal rupture occurred in seven patients (nine eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in three patients. Bilateral microcornea was present in one patient and two patients had a unilateral increased corneal diameter as a result of secondary glaucoma after trauma. Peripheral sclerocornea was present bilaterally in five patients. Curvature abnormalities included cornea plana, keratoconus, and keratoglobus.
Cornea 1993 Jan
PMID:Corneal abnormalities in Ehlers-Danlos syndrome type VI. 845 32

Keratoconus is a disease characterized by thinning and scarring of the central portion of the cornea. We have shown, in corneas and conjunctival tissues obtained from patients with keratoconus, that lysosomal enzyme staining is enhanced in the epithelial layer. In this study, we examined the lysosomal enzyme staining in skin-biopsy specimens of patients with keratoconus. Tissues collected from four patients with keratoconus and six normal subjects were fixed and processed for histochemical staining. Results showed that the epidermal and dermal layers of all skin specimens stained positively for two lysosomal hydrolases, acid esterase and acid phosphatase. The enzyme staining in the skin epidermal and dermal cells of the keratoconus patients was within the normal range. The staining in the corneal and conjunctival epithelia of the same patients was more prominent than that of normal controls. It appears that the biochemical abnormality identified in keratoconus is not manifested in the skin.
Cornea 1996 Jul
PMID:Normal lysosomal enzyme staining in skin tissues of patients with keratoconus. 877 67

Ulcerative colitis (Crohn's disease) is a chronic relapsing inflammatory bowel disease of unknown etiology. The most common ocular complications include conjunctivitis and uveitis, particularly iritis. Herein, we describe a patient who had a decrease in visual acuity due to an increasing astigmatism. This was accompanied with a peripheral limbal thinning of the cornea and faint confluent corneal changes. No systemic activity was present during the period that the patient was monitored. Changes of astigmatism were followed up with videokeratography. This apparatus monitors changes in clinical course accurately and makes comparison possible between separate visits.
Cornea 1997 Mar
PMID:Crohn's colitis and the cornea. 907 38

We report a case of Fuchs marginal keratitis with a recurrence and spontaneous perforation on the lamellar graft. A constellation of marginal corneal infiltrates and stromal thinning under a pseudopterygium characterize this condition. Two years after an initial lamellar keratoplasty, the pathology recurred within the graft. A repeat lamellar keratoplasty was performed, this time combined with a conjunctival autograft.
Cornea 2004 Aug
PMID:Recurrence of Fuchs marginal keratitis within a lamellar graft. 1525 7

Pellucid marginal corneal degeneration (PMCD) is managed surgically in the advanced stages of the disease, but extreme thinning extending over a very wide area in most of the corneal circumference represents a true surgical challenge that makes conventional approaches unsuitable. Here, we present the results of a new procedure (partial excision of the corneal ectasia and tuck of the residual thinned corneal lips left behind) performed in 3 eyes of 2 patients with extremely advanced PMCD, judged unsuitable for undergoing conventional surgical approaches. Preoperatively, uncorrected visual acuity was limited to the perception of hand motion in 1 eye, which presented with hydrops, and to finger counting at 1 m in the other 2 eyes. With a follow-up of 3 to 4 years, a complete, stable resolution of the ectasia was seen in all cases. As early as 1 year postoperatively, the best spectacle-corrected visual acuity was 20/30 to 20/50 with no subsequent substantial changes. Partial excision of the ectasia and tucking was found to work successfully at achieving both a new corneal shape compatible with visual rehabilitation and restoring peripheral corneal thickness in advanced cases of PMCD that were unsuitable for conventional surgery.
Cornea 2013 Dec
PMID:Combined tissue excision and corneal tuck for the surgical treatment of extremely advanced pellucid marginal corneal degeneration. 2416 53

Keratoconus (KC) is a non-inflammatory thinning and protrusion of the cornea in which the cornea assumes a conical shape. Complex etiology of this condition at present remains an enigma. Although environmental factors have been involved in KC pathogenesis, strong underlining genetic susceptibility has been proven. The lack of consistent findings among early genetic studies suggested a heterogeneity and complex nature of the genetic contribution to the development of KC. Recently, genome-wide linkage studies (GWLS) and genome-wide association studies (GWAS) were undertaken. Next-generation sequencing (NGS)-based genomic screens are also currently being carried out. Application of these recently developed comprehensive genetic tools led to a much greater success and increased reproducibility of genetic findings in KC. Involvement of the LOX gene identified through GWLS has been confirmed in multiple cohorts of KC patients around the world. KC susceptibility region located at the 2q21.3 chromosomal region near the RAB3GAP1 gene identified through GWAS was independently replicated. Rare variants in the ZNF469 gene (mutated in corneal dystrophy Brittle Cornea Syndrome) and in the TGFBI gene (mutated in multiple corneal epithelial-stromal TGFBI dystrophies) have been repeatedly identified in familial and sporadic KC patients of different ethnicities. Additional comprehensive strategies using quantitative endophenotypes have been successfully employed to bring further understanding to the genetics of KC. Additional genetic determinants including the COL5A1 gene have been identified in the GWAS of KC-related trait central corneal thickness. These recent discoveries confirmed the importance of the endophenotype approach for studying complex genetic diseases such as KC and showed that different connective tissue disorders may have the same genetic determinants.
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PMID:Genetics in Keratoconus: where are we? 2735 Sep 55


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