ABSTRACT
Choroidal neovascularization(CNV)is the ultimate pathological manifestation of various ocular diseases. Its pathogenesis is extremely complex and involves multiple cells, cytokines, and signaling pathways. MicroRNA(miRNA), as a kind of small biological molecules, is a non-coding RNA composed of 22 nucleotides that regulates gene expression by degrading or inhibiting mRNA translation of target genes. Having been increasingly studied and their involvement in the development of various diseases through miRNA-mediated signaling pathways have been revealed. In the field of ophthalmology, miRNA target specific protein genes through various signaling pathways to promote or inhibit CNV. Therefore, revealing the role and mechanism of miRNA in the pathogenesis of CNV is an important direction of future research on the pathogenesis of CNV. This article aims to review on phosphatidylinositol 3 kinase- protein kinase B(PI3K-Akt), transforming growth factor-beta(TGF-β), nuclear factor-kappa B(NF-κB), Notch and Wnt signaling pathways in miRNA regulation of CNV, providing new insights into the pathogenesis of CNV and targeted therapy for CNV.
ABSTRACT
PURPOSE: The objective of this study is to develop a tissue-engineered vascular graft using autologous bone marrow-derived cells (BMCs) and biodegradable polymer scaffold. METHOD: Autologous canine BMCs were isolated from bone marrow aspirate and cultured. A tubular scaffold was fabricated by immersing polyglycolic acid (PGA) sheet in poly (glycolide-co-caprolactone) (PGCL) solution and wrapping it around a cylindrical mold. The expanded BMCs were seeded onto the PGA/PGCL tubular scaffold (internal diameter: 7 mm, length: 35 mm) and further cultured in vitro for 1 week. The graft was anastomosed to the abdominal artery in a canine model. One week after implantation, the retrieved graft was investigated by histological and immunohistochemical analyses. RESULT: Cultured BMCs differentiated into endothelial-like and smooth muscle-like cells. The PGA tubular scaffold reinforced with PGCL was successfully implanted in an animal model without graft rupture. The vascular graft engineered with BMCs was occluded at 1 week after implantation due to thrombus formation. Histological and immunohistochemical analyses of the retrieved graft revealed that extracellular matrix proteins such as smooth muscle alpha-actin, smooth muscle myosin heavy chain and collagen were produced partially in the graft media. CoNCLUSION: The tissue-engineered vascular graft developed in this study led to graft failure due to early occlusion. Nevertheless, it is confirmed that the PGA/PGCL scaffold has microstructures appropriate for cell proliferation and good mechanical properties. This result suggests the possibile application of this scaffold as a material for engineering of diseased vascular tissues.