scholarly journals Mechanisms of Collagen Crosslinking in Diabetes and Keratoconus

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1239 ◽  
Author(s):  
McKay ◽  
Priyadarsini ◽  
Karamichos

Collagen crosslinking provides the mechanical strength required for physiological maintenance of the extracellular matrix in most tissues in the human body, including the cornea. Aging and diabetes mellitus (DM) are processes that are both associated with increased collagen crosslinking that leads to increased corneal rigidity. By contrast, keratoconus (KC) is a corneal thinning disease associated with decreased mechanical stiffness leading to ectasia of the central cornea. Studies have suggested that crosslinking mediated by reactive advanced glycation end products during DM may protect the cornea from KC development. Parallel to this hypothesis, riboflavin-mediated photoreactive corneal crosslinking has been proposed as a therapeutic option to halt the progression of corneal thinning by inducing intra- and intermolecular crosslink formation within the collagen fibrils of the stroma, leading to stabilization of the disease. Here, we review the pathobiology of DM and KC in the context of corneal structure, the epidemiology behind the inverse correlation of DM and KC development, and the chemical mechanisms of lysyl oxidase-mediated crosslinking, advanced glycation end product-mediated crosslinking, and photoreactive riboflavin-mediated corneal crosslinking. The goal of this review is to define the biological and chemical pathways important in physiological and pathological processes related to collagen crosslinking in DM and KC.


2019 ◽  
Vol 70 (4) ◽  
pp. 1152-1156
Author(s):  
Miruna Gabriela Burcel ◽  
Catalina Corbu ◽  
Valeria Coviltir ◽  
Vasile Potop ◽  
Mihaela Constantin ◽  
...  

Keratoconus is a progressive ectatic disorder characterised by irregular myopic astigmatism and loss of visual acuity due to corneal thinning. Corneal collagen crosslinking is the treatment recognised to stop the progression of keratoconus. Our study evaluates and compares visibility and depth of the stromal demarcation line after corneal collagen crosslinking using anterior segment optical coherence tomography between two groups:crosslinking with dextran-based and hydroxypropyl methylcellulose-based riboflavin solutions. Our work proved a better visibility and a deeper demarcation line when we used HPMC-based riboflavin. Also the study revealed that HPMC-based riboflavin is associated with better biomechanical outcomes than dextran-based riboflavin.



Author(s):  
B.E. Malugin ◽  
◽  
E.G. Solodkova ◽  
S.V. Balalin ◽  
V.S. Kulikov ◽  
...  

Purpose. To make a comparative analysis of topographic, tomographic and biomechanical values, measured by Pentacam HR and Corvis ST, in healthy multirefractive cohort versus patients with keratectasia of various severity. Material and methods. The prospective study comprised 237 patients aged from 18 to 47 years, subdivided into three groups. The first group included 174 healthy persons with various refraction (174 eyes). The second and the third group embraced 63 patients with keratoconus: 36 patients (36 eyes) with keratoconus of the I degree and 27 eyes with keratoconus of the II and III degrees. Besides the conventional comprehensive ocular examination the following studies were performed in all the patients: evaluation of topographic, tomographic and biomechanical corneal properties with application of Pentacam HR and Corvis ST (OCULUS Optikgerate GmbH; Wetzlar, Germany). Results. It was revealed that the following biomechanical values, assessed by means of Pentacam HR and Corvis ST, exhibited statistically significant changes (p<0,001) in all degrees of ketatoconus: a relative corneal thickness by Ambrosio, inverted radius of applanation curvature (IntRadius), DA Ratio Coefficient, values of corneal rigidity – SP-A 1 and SSI. Conclusion. The detected parameters may be applied as indicators, allowing to evaluate corneal biomechanics, to define early features of ectatic process, to assess effectiveness of the performed corneal collagen crosslinking and intralamellar keratoplasty with implantation of corneal segments. Key words: keratoconus, corneal biomechanics, pachymetry, index of pachymetric progression, corneal viscoelasticity.





2016 ◽  
Vol 73 (6) ◽  
pp. 572-576 ◽  
Author(s):  
Milorad Milivojevic ◽  
Vladimir Petrovic ◽  
Miroslav Vukosavljevic ◽  
Ivan Marjanovic ◽  
Mirko Resan

Background/Aim. Enlargement of optical zone (OZ) diameter during laser in situ keratomileusis (LASIK) correction of myopia postoperatively improves the optical outcome, however, it also leads to the increased stroma tissue consumption - progressive corneal thinning. The aim of this investigation was to present the possibility of safe OZ enlargement without impairing the structural stability of the cornea, while obtaining an improved optical outcome with LASIK treatment of shortsightedness. Methods. Preoperative assessment of the cornea structure and prediction of the ablated stroma tissue consumption was conducted in 37 patients (74 eyes) treated for shortsightedness by means of the LASIK method. With the eyes that, according to their cornea structure, had the capacity for OZ diameter enlargement of 0.5 mm, LASIK treatment was performed within the wider OZ diameter of 7.0 mm compared to the standard 6.5 mm. The following two groups were formed, depending on the diameter of the utilized OZ: the group I (the eyes treated with the OZ 6.5 mm, n = 37) and the group II (the eyes treated with the OZ 7.0 mm, n = 37). Results. No significant difference in the observed structural parameters of the cornea was detected between the groups of patients treated with different OZ diameters. The values of all the parameters were significantly bellow the threshold values for the development of postoperative ectasia. Conclusion. Diameter enlargement of the treated OZ, if there is a preoperative cornea capacity for such enlargement, will not impair the postoperative stability of the cornea structure, and will significantly improve the optical outcome.



2021 ◽  
Vol 8 ◽  
Author(s):  
Ceylan Onursal ◽  
Elisabeth Dick ◽  
Ilias Angelidis ◽  
Herbert B. Schiller ◽  
Claudia A. Staab-Weijnitz

In addition to providing a macromolecular scaffold, the extracellular matrix (ECM) is a critical regulator of cell function by virtue of specific physical, biochemical, and mechanical properties. Collagen is the main ECM component and hence plays an essential role in the pathogenesis and progression of chronic lung disease. It is well-established that many chronic lung diseases, e.g., chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) primarily manifest in the elderly, suggesting increased susceptibility of the aged lung or accumulated alterations in lung structure over time that favour disease. Here, we review the main steps of collagen biosynthesis, processing, and turnover and summarise what is currently known about alterations upon lung ageing, including changes in collagen composition, modification, and crosslinking. Recent proteomic data on mouse lung ageing indicates that, while the ER-resident machinery of collagen biosynthesis, modification and triple helix formation appears largely unchanged, there are specific changes in levels of type IV and type VI as well as the two fibril-associated collagens with interrupted triple helices (FACIT), namely type XIV and type XVI collagens. In addition, levels of the extracellular collagen crosslinking enzyme lysyl oxidase are decreased, indicating less enzymatically mediated collagen crosslinking upon ageing. The latter contrasts with the ageing-associated increase in collagen crosslinking by advanced glycation endproducts (AGEs), a result of spontaneous reactions of protein amino groups with reactive carbonyls, e.g., from monosaccharides or reactive dicarbonyls like methylglyoxal. Given the slow turnover of extracellular collagen such modifications accumulate even more in ageing tissues. In summary, the collective evidence points mainly toward age-induced alterations in collagen composition and drastic changes in the molecular nature of collagen crosslinks. Future work addressing the consequences of these changes may provide important clues for prevention of lung disease and for lung bioengineering and ultimately pave the way to novel targeted approaches in lung regenerative medicine.



Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Luigi Di Biase ◽  
Aaron Baker ◽  
Xue Yan ◽  
Jason Lee ◽  
Francesco Santoro ◽  
...  

Introduction: Catheter ablation of atrial fibrillation (AF) is the most valid therapeutic option to achieve rhythm control. Pulmonary veins (PV) are the most known trigger of AF, although recently we have become more aware of the importance of non-PV triggers. Expression of microRNA (miRNA) has been shown to be regulated in many cardiovascular disease. We sought to study expression patterns of miRNA in patients (pts) with AF undergoing ablation to facilitate their application as both diagnostic and prognostic markers. Methods: As part of the standard procedure for AF ablation a double transseptal sample of myocardial tissue is obtained via a transseptal needle. The small piece of atrial septal tissue can be retrieved from the needle as a result of piercing the atrial septum. MiRNA was hybridized to microarrays to determine relative levels of miRNAs in the samples. For a subset of the miRNAs we validated expression through quantitative real time PCR. All pts underwent PV-antrum and non-PV trigger ablation guided by isoproterenol challenge test. Results: Atrial tissue of 11 pts undergoing AF ablation has been utilized for MiRNA assessment. Mean age was 61.27 ± 10.5 years and 8 (72.7%) pts were male. Six (54.5 %) pts had paroxysmal AF. During the ablation non-PV triggers were detected in 8 (72.7 %) pts. Recurrence of AF occurred in 3(27.3 %) pts. Expression of miR-21, miR-26a and miR-29a was higher in pts with non-PV triggers, while miR-30c had lower expression in pts who had recurrence of atrial tachyarrhythmias. Spearman’s nonparametric correlation coefficient was calculated and miR-21, miR-26a, miR-29a were positively correlated with non-PV triggers (r = 0.58, p=0.06 for all three miRNAs), while miR-30c level had inverse correlation (r = (-) 0.78 %, p=0.005) with recurrence (Figure). Conclusions: Expression of miR-21, miR-26a, miR-29a correlates with the presence of non-PV triggers. This information could be clinically relevant in planning patient specific procedures.



1986 ◽  
Vol 14 (3) ◽  
pp. 237-243 ◽  
Author(s):  
David F. Counts ◽  
Susan Shull ◽  
Kenneth R. Cutroneo


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254198
Author(s):  
Tássia Kirchmann Lazzari ◽  
Erika Cavalheiro ◽  
Sandra Eugênia Coutinho ◽  
Lívia Fontes da Silva ◽  
Denise Rossato Silva

Introduction The pathogenesis of consumptive syndrome of tuberculosis (TB) is largely unknown. Leptin concentrations may be high because of the host’s inflammatory response, contributing to weight loss in patients with TB. The receptor for advanced glycation end products (RAGE) is also associated with weight loss in patients with TB and is related to enhanced mortality. The objective of this study was to evaluate the association between leptin and AGE/RAGE. Methods Case-control study. Leptin, AGE (carboxymethyl lysine, CML) and soluble RAGE (sRAGE) were measured from blood samples by ELISA. Results We included in the study 34 patients with TB and 34 controls. We found an inverse correlation between serum leptin levels and sRAGE, only in cases (r = -0.609, p < 0.0001). sRAGE levels were lower in patients with TB who died as compared with patients who survive (21.90 ± 4.24 pg/mL vs 66.14 ± 29.49 pg/mL; p = 0.045). Leptin levels were higher in patients with TB who died as compared with patients who survive (14.11 [7.48–14.11] ng/mL vs 3.08 [0.54–6.34] ng/mL; p = 0.028). Conclusions We identified lower sRAGE levels and higher leptin levels in patients with TB who died as compared with patients who survive. In addition, an inverse and significant correlation between serum leptin and sRAGE levels was demonstrated. Future studies, with a larger sample size and in different settings, including not only hospitalized patients, are needed to confirm these findings.



2021 ◽  
pp. 21-25
Author(s):  
M.M. Bikbov ◽  
◽  
V.K. Surkova ◽  
G.М. Kazakbaeva ◽  
◽  
...  

Purpose. To study morphological changes in the cornea by confocal microscopy of simultaneous MyoRing implantation with corneal crosslinking in patients with keratoconus. Material and methods. The clinical study included 15 patients (16 eyes) with progressive keratoconus. All patients underwent a combination treatment: implantation of MyoRing intrastromal corneal rings (Dioptex GmBH, Linz, Austria) in combination with corneal crosslinking. The number of cells and quality indicators in each layer of the cornea were compared before and during 36 months after surgery. Results. Qualitative analysis of the cornea showed transient disturbances of the subepithelial nerve plexus, an increase in the reflectivity of stromal keratocytes, and moderate fibroplasia in the middle parts of the stroma in the area of the intrastromal pocket. During the follow-up period of 12 months or more after surgery, no significant changes in the corneal ultrastructure were detected in the dynamics. There was no significant decrease in endothelial cell density in the postoperative period. Conclusion. Analysis of morphological changes confirms the safety of a combination of simultaneous implantation of the MyoRing intrastromal ring and corneal crosslinking in stage II-III keratoconus by confocal microscopy and allows dynamic observation of changes in the corneal structure during intrastromal surgery. Key words: keratoconus, confocal microscopy, intrastromal corneal rings, MyoRing, corneal crosslinking.



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