RESUMO
Retinal neovascularization (RNV) is a type of serious visionthreating disease, commonly induced by hypoxia of ischemic retinopathy, which happens in various ocular diseases including diabetic retinopathy and retinopathy of prematurity. In clinical work, antiVEGF therapy is the preferred strategy for treating RNV. However, not all cases are sensitive to antiVEGF injection. It is urgent and necessary to develop novel targets for inhibiting neovascularization in ocular diseases. Angiogenin (ANG) and brainderived 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 noncoding RNA, which can modulate targets by degrading transcripts or inhibiting protein translation. In the present study, miRNAmediated modulation of ANG and BDNF was explored in an oxygeninduced retinopathy mouse model and human retinal microvascular endothelial cells (HRECs) under hypoxia. The results showed that downregulation of miR1825p and upregulation of ANG and BDNF were found in vivo and in vitro. Overexpression of miR1825p suppressed the expression of ANG and BDNF significantly in HRECs under hypoxia. In addition, knockdown of ANG and BDNF by miR1825p transfection significantly improved hypoxiainduced HRECs dysfunctions, including enhancing cell viability, reducing cell migration and improved tube integrity. In conclusion, miRNAdependent regulation on ANG and BDNF indicates a critical role in hypoxiainduced retinal microvascular response. miR1825pbased therapy can influence the expression of ANG and BDNF, which demonstrates the potential for treating RNV diseases.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , MicroRNAs/metabolismo , Neovascularização Retiniana/metabolismo , Ribonuclease Pancreático/metabolismo , Animais , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Oxigênio/metabolismo , Gravidez , Neovascularização Retiniana/genética , Vasos RetinianosRESUMO
Macular hemorrhage can occur spontaneously and repeatedly without choroidal neovascularization or other known lesions associated with myopia. We report a case of repeated myopic macular hemorrhage following fish oil supplementation. A 32-year-old male was referred with newly acquired paracentral scotoma in the left eye. Serial retinal imaging, including fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography were performed. Fundus photography and fluorescein angiography showed a subtle red-colored lesion nasal to the fovea. Optical coherence tomography showed a dome shaped elevation in the ellipsoid zone and interdigitation zone in the left eye. No known ocular risk factors for macular hemorrhage, such as choroidal neovascularization, lacquer cracks, Fuch's spot or choroid thinning or keratoconus were observed. After 2 months without any treatment, the left eye lesion disappeared. However 2 weeks later, another newly developed red-colored lesion close to the left fovea was observed. At that moment, the detailed medical history revealed that the patient had been regularly taking a high dose of commercially available fish oil supplement beginning one month before the first macular hemorrhage. After discontinuation of the fish oil, the second left hemorrhage resolved gradually over the following 8 weeks. No recurrent hemorrhages have been detected at the 12 months follow-up visits. Our observations suggest that the relative value of nutritional supplementation with high doses of fish oil should be cautioned in patients with repetitive retinal hemorrhage.