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@#As a newly discovered endogenous regulator, fibroblast growth factor 21(FGF21)becomes hot topic in recent professional research. It plays an important role in diabetic retinopathy recently. Moreover, FGF21 has attracted more and more attention in recent years. This paper discussed the molecular structure of FGF 21, biological function, relationship between FGF21 and inflammatory response and role in the pathological process of diabetic retinopathy.
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Objective • To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods • The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results • Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models(P<0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion • ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.
ABSTRACT
Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models (P＜0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.
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Neovascular eye diseases,with highly complicated and refractory,are one group of the most difficult problems for domestic and overseas clinical oculists in recent years.Angiogenesis is a complex process participating with multiple factors and various ways,and its exact pathogenesis is unclear yet.Ocular neovascularization is the dynamic balance result between proangiogenic factors and antiangiogenic factors provided that intraocular microenvironment be under a physiological condition.Some pathological factors including ischemia,hypoxia and inflammation destroy the dynamic balance between cytokines leading to neovascularization.Currently studies indicated that numerous cytokines containing vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) are closely linked to ocular neovascularization,while it is more crucial to elucidate the molecular mechanism of numerous cytokines involved in ocular neovascularization,which can recognize the pathogenesis of neovascular eye disease more clearly.Research progress of pathological relevant cytokines of neovascular eye diseases,including VEGF,insulin-like growth factor 1 (IGF-1),angiogenin-2 (Ang-2),stromal cell derived factor 1 (SDF-1) and PEDF were reviewed in this paper.
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Diabetic retinopathy (DR) is a common disease of ophthalmology,often causes irreversible decline of patients' vision,which has two features including macular oedema,diabetic retinal neovascularization.Diabetic retinal neovascularization is one of the most important reasons leading to blindness.Endostatin (ES) is one of the most effective agents inhibiting angiogenesis,whose biological function has a close relationship with its chemical construction.However,its mechanisms of treating diabetic retinal neovascularization are very complicated and remain unclear.Therefore,in this review we summarized several possible mechanisms,including regulating the expression of extracellular matrix,inhibiting the expression of pro-angiogenic factors,and regulating the signaling pathways,by which ES may inhibiting diabetic retinal neovascularization.
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Neovascularization is the main cause of blindness, such as diabetic retinopathy, retinopathy of prematurity and age - related macular degeneration. Vascular endothelial growth factor( VEGF) plays an important role in the formation of angiogenesis, and is considered to be the most potent angiogenic growth factor. Placental Growth Factor(PlGF) is one of the VEGF family, which play a crucial role in endothelial cell proliferation and migration, angiogenesis, and immune - mediated inflammation. Meanwhile, PlGF is specifically expressed in pathological angiogenesis, but not in normal blood vessels. In recent years, there has been increasing attention to PlGF, therefore this article reviews the role of PlGF in neovascular ocular diseases.
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MicroRNAs(miRNAs) are a type of highly conserved,small non-coding RNAs,which powerfully regulate gene expression at the posttranscriptional level.In humans,it modulates about 30％ of protein coding genes.Ocular neovascularization is one of the most important clinical problems in ophthalmology and a common cause of blindness.Recent studieshavedemonstrated that miRNAs play a crucial rolein the development of ocular neovascularization.The use of miRNAs provides novel therapeutic approaches for ocular neovascularization.Here,we describe our understanding of the functions and expressions of miRNAs in eyes,the relationship among miRNAs,ocular neovascularization and angiogenic factors,and the current research of miRNAs in diabetic retinopathy.
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Endostatin(ES), the C-terminal fragment of collagen XVIII, is a potent angiogenesis inhibitor. At present, there are a large number of research papers on ES. It has already been on clinical stage Ⅱ and been widely used in inhibition of neovascularization(NV). However, how to improve the bioactivity of ES is still a matter of ongoing discussion. The objective of this review is to elucidate the relationship between the modified ES and ocular neovascualrization, and to discuss the superiority based on the structure modification. The structure can be changed either by covalent modification or by genetical mutation. It is proposed that the secondary structral ES enhance the anti-angiogenic activity. Studies on modified ES also shed light on our understanding of the molecular action mechanisms of ES. Modified ES may be exploited as a new angiogenesis inhibitor for therapeutic applica-tions, in substitution of the native ES. Activity