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Purpose: To investigate the expression of CD146 and its role in proliferative diabetic retinopathy (PDR). Methods: Enzyme linked immunosorbent assay was performed to analyse the expression and relationship of sCD146, vascular endothelial growth factor (VEGF), sVEGFR1 and sVEGFR2 in vitreous specimens from PDR and idiopathic epiretinal membranes (IERM) or idiopathic macular hole patients. The location of CD146 in ERMs was detected by immunofluorescence. The oxygen‐induced retinopathy (OIR) mice model was established and the adeno‐associated virus expressing a shRNA of CD146 (AAV1‐shCD146‐GFP) was administered via intravitreal injection. The effect of AAV1‐shCD146‐GFP was explored by immunofluorescence, Western blot and quantitative real‐time PCR. Results: The levels of sCD146 in vitreous specimens from PDR patients and CD146 in retinas from OIR mice were significantly increased. Immunofluorescence showed that CD146 was co‐located with CD31, VEGF, VEGFR1 and VEGFR2, respectively. Intravitreal injection of AAV1‐shCD146‐GFP could dramatically reduce the formation of neovascularization and non‐perfusion area by inhibiting VEGFR2 phosphorylation. Conclusion: Our results indicated that CD146 was involved in the development of retinal neovascularization via VEGFR2 pathway. Anti‐CD146 may be an innovative or adjuvant therapy, which provides a new direction for the treatment of PDR and other ocular neovascular diseases. [ABSTRACT FROM AUTHOR]

Choroidal neovascularization (CNV) is an important characteristic of advanced wet age‐related macular degeneration (AMD) and leads to severe visual impairment among elderly patients. Previous studies have demonstrated that melatonin induces several biological effects related to antioxidation, anti‐inflammation, and anti‐angiogenesis. However, the role of melatonin in CNV, and its underlying mechanisms, has not been investigated thus far. In this study, we found that melatonin administration significantly reduced the scale and volume of CNV lesions, suppressed vascular leakage, and inhibited the capacity of vascular proliferation in the laser‐induced mouse CNV model. Additionally, the results also show that the melatonin‐treated retinal microglia in the laser‐induced mice exhibited enhanced expression of M1‐type markers, such as iNOS, CCL‐3, CCL‐5, and TNF‐α, as well as decreased production of M2‐type markers, such as Arg‐1, Fizz‐1, IL‐10, YM‐1, and CD206, indicating that melatonin switched the macrophage/microglia polarization from pro‐angiogenic M2 phenotype to anti‐angiogenic M1 phenotype. Furthermore, the RhoA/ROCK signaling pathway was activated during CNV formation, yet was suppressed after an intraperitoneal injection of melatonin. In conclusion, melatonin attenuated CNV, reduced vascular leakage, and inhibited vascular proliferation by switching the macrophage/microglia polarization from M2 phenotype to M1 phenotype via inhibition of RhoA/ROCK signaling pathway in CNV. This suggests that melatonin could be a novel agent for the treatment of AMD. [ABSTRACT FROM AUTHOR]

Abstract: Retinopathy of prematurity (ROP) is a retinopathy characterized by retinal neovascularization (RNV) occurring in preterm infants treated with high concentrations of oxygen and may lead to blindness in severe cases. Currently, anti‐VEGF therapy is a major treatment for ROP, but it is costly and may cause serious complications. The previous study has demonstrated that melatonin exerted neuroprotective effect against retinal ganglion cell death induced by hypoxia in neonatal rats. However, whether melatonin is anti‐angiogenic and neuroglial protective in the progression of ROP remains unknown. Thus, this study was to investigate the effect of melatonin on RNV and neuroglia in the retina of oxygen‐induced retinopathy (OIR) mice. The results showed a reduction in retinal vascular leakage in OIR mice after melatonin treatment. Besides, the size of retinal neovascular and avascular areas, the number of preretinal neovascular cell nuclei, and the number of proliferative vascular endothelial cells within the neovascular area were significantly decreased in mice treated with melatonin. After oxygen‐induced injury, the density of astrocytes was decreased, accompanied by morphologic and functional changes of astrocytes. Besides, retinal microglia were also activated. Meanwhile, the levels of inflammatory factors were elevated. However, these pathologic processes were all hindered by melatonin treatment. Furthermore, HIF‐1α‐VEGF pathway was activated in the retina of OIR mice, yet was suppressed in melatonin‐treated OIR mice retinas. In conclusion, melatonin prevented pathologic neovascularization, protected neuroglial cells, and exerts anti‐inflammation effect via inhibition of HIF‐1α‐VEGF pathway in OIR retinas, suggesting that melatonin could be a promising therapeutic agent for ROP. [ABSTRACT FROM AUTHOR]

Objective: In the present study, we investigated the effects of Magnolol on the retinal neovascularization (RNV) and local glial cells in an oxygen-induced retinopathy (OIR) model and explored their molecular mechanisms. Materials and methods: Neonatal C57BL/6J mice were subjected to 75 % O ± 5 % from postnatal day (P) 7 to P12 and subsequently returned to room air. Mice were injected with 25 mg/kg Magnolol intraperitoneally once a day from P12 to P17, then retinas were harvested and flat-mounted to assess the retinal vessels, astrocytes and microglia. To clarify the molecular mechanisms of Magnolol, we observed the level of inflammatory cytokines such as interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, and analyzed the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) pathway in OIR mice. Results: Intraperitoneal administration of Magnolol resulted in significant reduction of RNV without retinal toxicity or perturbation of developmental retinal angiogenesis. In addition, Magnolol preserved the astrocyte morphology and diminished the activation of microglia. Moreover, Magnolol down regulated the expression of inflammatory cytokines and inactivated the HIF-1α/VEGF pathway. Conclusions: These results indicated that Magnolol might have potential for the treatment of pathological retinal angiogenesis and glial dysfunctions via anti-inflammation and inhibition of HIF-1α/VEGF pathway. [ABSTRACT FROM AUTHOR]