Evaluation of collagen derived antiangiogenic factors and matrix metalloproteinases in anterior lens epithelial cells of pediatric eyes with persistent fetal vasculature

Abstract

Purpose:To measure levels of collagen-derived antiangiogenic factors (arresten, canstatin, tumstatin, endostatin) and matrix metalloproteinases (MMP-2 and MMP-9) in anterior lens epithelial cells (LECs) and anterior capsules of children with cataract and persistent fetal vasculature (PFV) as cases and cataract without PFV as controls.Methods:Anterior capsules harboring LECs were collected from pediatric cataract patients with (n = 13) and without PFV (n = 13) during surgery. Samples were immediately subjected to RNA extraction and cDNA preparation. Quantitative real time PCR was performed to determine the mRNA levels of antiangiogenic factors and matrix metalloproteinases. GAPDH (Glyceraldehyde 3-Phosphate Dehydrogenase) and β Actin were used as the housekeeping control. The mRNA levels were expressed as a ratio, using the delta-delta method for comparing the relative expression results between controls and cases. The non-parametric Mann-Whitney U test was applied for statistical evaluation. P values < 0.05 were statistically significant.Results:The relative mRNA levels of arresten, canstatin, tumstatin, endostatin, MMP-2 and MMP-9 in cases were 6.20E-03 ± 0.003, 1.49E-01 ± 0.02, 1.70E-01 ± 0.007, 3.20E-03 ± 0.003, 1.11E-03 ± 0.0009 and 3.72E-04 ± 0.0001. The mRNA levels of arresten was 1.6 times lower (P = 0.01) while mRNA levels of MMP-2, tumstatin and canstatin were 4, 2.5, and 2.3 times higher in cases than in controls. No change was observed in mRNA levels of MMP-9 and endostatin (P = 0.82).Conclusion:A significant difference in the levels of arresten, canstatin, tumstatin, and MMP-2 was found in LECs with PFV.

Bevacizumab as adjunctive therapy in anterior persistent fetal vasculature

“…Although the exact pathogenesis of PFV is unknown, VEGF and placental growth factor have been reported to play a role in hyaloid vasculature regression and the development of PFV. Gajjar and colleagues 4 proposed that an imbalance in the levels between antiangiogenic factors such as arresten and matrix metalloproteinases may play a role in the development of PFV.…”

Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy

“…The cleaved off N-propeptide is a non-collagenous fragment that is also known as arresten which acts as angiogenesis inhibitor [ 101 , 102 ]. Arresten inhibits endothelial cell proliferation, migration and tube formation and reduces subcutaneous tumor growth in mice and suppresses squamous cell carcinoma invasion [ 101 – 103 ].…”

Association between MMP-2 gene polymorphism and cataract susceptibility

“…[ 17 , 18 ] Finally, it could result in matrix contracture, cell aggregation, collagen deposition, posterior capsule wrinkling, and opacity. [ 19 , 20 ] Therefore, MMP-2 protein that is formed after the transcriptional translation of MMP-2 gene may be related to the occurrence and development of cataract. [ 21 , 22 ]…”