angiogenin and Retinal-Neovascularization

Retinal neovascularization (RNV) is a type of serious vision‑threating disease, commonly induced by hypoxia of ischemic retinopathy, which happens in various ocular diseases including diabetic retinopathy and retinopathy of prematurity. In clinical work, anti‑VEGF therapy is the preferred strategy for treating RNV. However, not all cases are sensitive to anti‑VEGF injection. It is urgent and necessary to develop novel targets for inhibiting neovascularization in ocular diseases. Angiogenin (ANG) and brain‑derived neurotrophic factor (BDNF) are implicated in angiogenesis, although their regulation and effects in RNV remain to be elucidated. microRNA (miRNA) is a type of small non‑coding RNA, which can modulate targets by degrading transcripts or inhibiting protein translation. In the present study, miRNA‑mediated modulation of ANG and BDNF was explored in an oxygen‑induced retinopathy mouse model and human retinal microvascular endothelial cells (HRECs) under hypoxia. The results showed that downregulation of miR‑182‑5p and upregulation of ANG and BDNF were found

Topics: Animals; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Endothelial Cells; Female; Gene Expression Regulation; Humans; Hypoxia; Mice; Mice, Inbred C57BL; MicroRNAs; Neovascularization, Pathologic; Oxygen; Pregnancy; Retinal Neovascularization; Retinal Vessels; Ribonuclease, Pancreatic

Retinal neovascularization, which is the pathological growth of new blood vessels, is associated with retinopathy of prematurity, neovascular age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. In this study, we evaluated the effect of an extract of Cnidium officinale Makino (COE) and its bioactive compound, butylidenephthalide (BP), on the migration and tube formation of human umbilical vein endothelial cells (HUVECs), and on retinal pathogenic neovascularization in the oxygen-induced retinopathy (OIR) mouse model.. The HUVECs were incubated with COE and BP (0.1-10 μg/ml). The mice were exposed to 75 % oxygen for 5 days starting on the 7(th) postnatal day (P7-P12). Then, the mice were returned to room air and intraperitoneally injected with COE (100 mg/kg) and BP (5 mg/kg) once per day for 5 days (P12-P16). On P17, we measured retinal neovascularization and analyzed the angiogenesis-related proteins expression using protein arrays.. COE and BP inhibit the HUVECs migration and the tube formation in a dose-dependent manner. In addition, COE significantly decreased retinal neovascularization in the OIR mice. COE reduced the expression levels of AREG, ANG, DLL4, Endostatin, IGFBP-2 and VEGF. Additionally, BP also inhibited the retinal neovascularization and down-regulated the expression of AREG, ANG, DLL4 and VEGF.. These results suggest that COE and BP exerts antiangiogenic effects on retinal neovascularization by inhibiting the expression of AREG, ANG, DLL4 and VEGF, indicating that antiangiogenic activities of COE may be in part due to its bioactive compound, BP.

Topics: Animals; Cell Movement; Cells, Cultured; Cnidium; Human Umbilical Vein Endothelial Cells; Humans; Mice; Phthalic Anhydrides; Plant Extracts; Retinal Neovascularization; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A

Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxidant, and anti-cancer properties. This study sought to determine the protective effects of chrysin on retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM glucose-exposed human retinal endothelial cells and in db/db mouse eyes. High glucose caused retinal endothelial apoptotic injury, which was inhibited by submicromolar chrysin. This compound diminished the enhanced induction of HIF-1α, vascular endothelial growth factor (VEGF), and VEGF receptor-2 (VEGFR2) in high glucose-exposed retinal endothelial cells. Consistently, oral administration of 10 mg/kg chrysin reduced the induction of these proteins in db/db mouse eye tissues. In addition, chrysin restored the decrement of VE-cadherin and ZO-1 junction proteins and PECAM-1 in hyperglycemia-stimulated retinal endothelial cells and diabetic mouse retina, possibly maintaining tight cell-cell interactions of endothelial cells and pericytes. Anti-apoptotic chrysin reduced the up-regulation of Ang-1, Ang-2, and Tie-2 crucial to retinal capillary occlusion and BRB permeability. Furthermore, orally treating chrysin inhibited acellular capillary formation, neovascularization, and vascular leakage observed in diabetic retinas. These observations demonstrate, for the first time, that chrysin had a capability to encumber diabetes-associated retinal neovascularization with microvascular abnormalities and BRB breakdown.

Topics: Animals; Antigens, CD; Apoptosis; Cadherins; Diabetic Retinopathy; Flavonoids; Glucose; Humans; Hyperglycemia; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mice; Mice, Inbred C57BL; Platelet Endothelial Cell Adhesion Molecule-1; Receptor, TIE-2; Retinal Neovascularization; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Zonula Occludens-1 Protein

The vitreous levels of angiogenin, which is a potent blood vessel-inducing protein, were measured to determine their association with proliferative diabetic retinopathy (PDR). Undiluted vitreous fluid specimens were collected from 30 eyes with PDR at the time of vitrectomy. A sandwich enzyme-liked immunosorbent assay was then used to quantitate the levels of angiogenin. As a control we determined the levels in the specimens from 21 patients with proliferative vitreoretinopathy (PVR) and 4 patients with idiopathic macular epiretinal membrane (IERM). The average angiogenin level in the eyes with PDR was 43.7 ng/ml, and no significant difference was observed among PDR, PVR and their reoperation cases. In the category of IERM, the mean concentration of angiogenin was 2.1 ng/ml, which was significantly lower than that of the PDR and PVR cases. Our study thus demonstrated a significant increase in the vitreous angiogenin levels in eyes with PDR, PVR and those undergoing reoperation for these conditions in comparison to eyes with IERM. We therefore postulated that the elevated angiogenin levels thus reflected a breakdown of the blood-ocular barrier in eyes with PDR and PVR.

Topics: Adult; Aged; Angiogenesis Inducing Agents; Blood-Retinal Barrier; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Female; Humans; Macular Degeneration; Male; Middle Aged; Proteins; Retinal Neovascularization; Ribonuclease, Pancreatic; Vitreoretinopathy, Proliferative; Vitreous Body