Abnormalities of the Extracellular Matrix in Keratoconus Corneas

Kenney, M. Cristina; Nesburn, Anthony B.; Burgeson, Robert E.; Butkowski, Ralph J.; Ljubimov, Alexander V.

doi:10.1097/00003226-199705000-00016

Cited by 162 publications

(120 citation statements)

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“…19,21,29 In the studied corneas, some BM components but not others were indeed detected around INTACS channels. An interesting example concerns nidogens.…”

Section: Discussionmentioning

confidence: 76%

“…The main differences in the expression of ECM proteins and proteinases were seen outside the INTACS area and were more pronounced in keratoconus, in agreement with our previous results. 29 Despite mild histopathologic changes around INTACS channels, 16,37 significant accumulation of several fibrotic ECM markers was observed in these areas. Similar deposits were detected in radial keratotomy scars, 21 in cases of failed LASIK, 19,30 and in scarred areas of keratoconus corneas.…”

Section: Discussionmentioning

confidence: 95%

“…Similar deposits were detected in radial keratotomy scars, 21 in cases of failed LASIK, 19,30 and in scarred areas of keratoconus corneas. 29 They may be related to a wound healing process that may be incomplete even years after surgically induced stromal injury, 21 despite the attempts of corneal cells to remove abnormal ECM deposits by secreted proteinases.…”

Section: Discussionmentioning

confidence: 99%

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Alterations of Extracellular Matrix Components and Proteinases in Human Corneal Buttons With INTACS for Post-Laser In Situ Keratomileusis Keratectasia and Keratoconus

Maguen¹,

Rabinowitz²,

Regev³

et al. 2008

Cornea

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Purpose-To perform an immunohistochemical evaluation of corneas with INTACS for post-laser in situ keratomileusis (LASIK) keratectasia and keratoconus, obtained after corneal transplantation.Methods-Corneas from 1 patient with INTACS for post-LASIK keratectasia and 2 patients with INTACS for keratoconus were obtained within 3 hours after penetrating keratoplasty, and cryostat sections were analyzed by immunostaining for 35 extracellular matrix (ECM) components and proteinases.Results-In the stroma of all corneas next to an INTACS implant, ECM components typically associated with fibrosis were observed. These included tenascin-C, fibrillin-1, and types III, IV (α1/ α2 chains), and XIV collagen. Also, significant deposition of perlecan, nidogen-2, and cellular fibronectin was revealed in the same locations. The keratoconus cases displayed typical Bowman layer breaks and subepithelial fibrosis with deposition of various ECM components. In all cases, some keratocytes around INTACS were positive for specific proteinases associated with stromal remodeling, including cathepsins F and H, matrix metalloproteinase (MMP)-1, MMP-3, and MMP-10. Staining for MMP-7 was variable; MMP-2 and MMP-9 were mostly negative. Patterns of type IV collagen α3, α4, and α6 chains; types VI and VIII collagen;α4, α5,β1, β2, and γ1 laminin chains; vitronectin; thrombospondin-1; urokinase; EMMPRIN; and cathepsins B and L were unchanged around INTACS in all 3 cases compared with normal. Recently, INTACS has acquired new interest as an alternative treatment of keratoconus. [5][6][7][8][9][10] The rationale is that INTACS not only flattens the central cornea but also corrects some of the astigmatic component. The corneal profile becomes more symmetrical, usually allowing better correction with glasses and contact lenses. Given that, for these patients, the alternative would be penetrating keratoplasty, INTACS may delay the need for this option. 10,11 Midstromal semicircular channels for INTACS ring insertion are created by a mechanical system with a blunt spiral device. 1,12,13 Despite the streamlined mechanistic procedure, attempts were made to improve control over the depth and shape of the channels. A femtosecond laser mounted on a delivery system capable of creating an intrastromal pattern of virtually any shape was recently used to create channels for INTACS insertion. 10 This method may be technically easier and more precise, reflecting better final outcomes. Conclusions-AbnormalKeratectasia is a rare but serious complication of laser vision correction of any refractive errors. It occurs mostly after LASIK but was also described after surface excimer laser ablation (photorefractive keratectomy). 14-16 It involves severe refractive changes mostly occurring several years after the surgery, which are caused by thinning and sagging of the corneal profile, similar to keratoconus.The etiology of this complication remains uncertain. In some cases, preexisting forme fruste keratoconus was documented. 17,18 Other cases could be caused by a me...

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“…19,21,29 In the studied corneas, some BM components but not others were indeed detected around INTACS channels. An interesting example concerns nidogens.…”

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Alterations of Extracellular Matrix Components and Proteinases in Human Corneal Buttons With INTACS for Post-Laser In Situ Keratomileusis Keratectasia and Keratoconus

Maguen¹,

Rabinowitz²,

Regev³

et al. 2008

Cornea

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“…It has been suggested that thinning of the cornea may be due to defective formation or destruction of the extracellular matrix as a consequence of altered or abnormal levels of fibronectin and type VI collagen. 3 In the early stages of KC, the cell membrane is disrupted, the basal cell layer disappears, 4 and particulate material is deposited between the surface of basal epithelial cells and Bowman's layer. 5 As the basal cells degenerate, they may release proteolytic enzymes, which can destroy underlying tissue.…”

Section: Introductionmentioning

confidence: 99%

Changes in tear protein profile in keratoconus disease

Acera

Vecino

Rodríguez-Agirretxe³

et al. 2011

Eye

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Purpose To analyze tear protein profile variations in patients with keratoconus (KC) and to compare them with those of control subjects. Subjects and methods Tears from 12 normal subjects and 12 patients with KC were analyzed by two-dimensional gel electrophoresis (2-DE) and liquid chromatography-mass spectrometry (LC-MS). Analysis of the 2-DE gels was performed using Progenesis SameSpots software (Nonlinear Dynamics). Proteins exhibiting high variation in expression levels (P-value o0.05) were identified using matrix-assisted laser desorption/ionization-TOF spectrometry. For LC-MS analysis, a label-free quantification approach was used. Tears were digested with trypsin, subjected to data-independent acquisition (MS E ) analysis, and identified proteins were relatively quantified using ProteinLynx Global Server software (Waters). Results The 2-DE and LC-MS analyses revealed a significant decrease in the levels of members of the cystatin family and an increase in lipocalin-1 in KC patients. A 1.43-fold decrease was observed for cystatin-S by 2-DE, and 1.69-and 1.56-fold for cystatin-SN and cystatin-SA by LC-MS, respectively. The increase in lipocalin-1 was observed by both methods with fold changes of 1.26 in the 2-DE approach and 1.31 according to LC-MS. Significant protein upregulation was also observed for Ig-j chain C and Ig J chain proteins by 2-DE. Levels of lipophilin-C, lipophilin-A, and phospholipase A2 were decreased in tears from KC patients according to LC-MS. Serum albumin was found to be increased in KC patients according to LC-MS. Conclusion The results show differences in the tear protein profile of KC and control subjects. These changes are indicative of alterations in tear film stability and in interactions with the corneal surface in KC patients.

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“…Biochemical and immunohistochemical studies of the matrix's proteoglycans show differences between normal and keratoconic corneas [5]- [8]. Enzymatic alterations with an increased expression proteolytic enzymes, [6] [9]- [11] decreased concentration of protease inhibitors [9] [12] and modified configuration of the stromal collagen lamella [13] have been observed.…”

Section: Introductionmentioning

confidence: 99%

Corneal Cross Linking with Riboflavin for Progressive Keratoconus in Paediatric Eyes

Nawani¹,

Jain²,

Singh³

2014

OJOph

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Purpose: To report visual, refractive and topographic outcomes after corneal collagen crosslinking (CXL) for progressive keratoconus in paediatric eyes. Methods: In this prospective interventional study, twenty eyes of eighteen patients with progressive keratoconus were included. All eyes underwent CXL with riboflavin after documented progression of the disease. Informed, written consent was taken from the parents of the patients. The patients were followed up for 6 mon-

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Abnormalities of the Extracellular Matrix in Keratoconus Corneas

Cited by 162 publications

References 0 publications

Alterations of Extracellular Matrix Components and Proteinases in Human Corneal Buttons With INTACS for Post-Laser In Situ Keratomileusis Keratectasia and Keratoconus

Alterations of Extracellular Matrix Components and Proteinases in Human Corneal Buttons With INTACS for Post-Laser In Situ Keratomileusis Keratectasia and Keratoconus

Changes in tear protein profile in keratoconus disease

Corneal Cross Linking with Riboflavin for Progressive Keratoconus in Paediatric Eyes

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