The Correlation Study Of Morphological Changes In Diabetic Retinal Vessels With Expression Of VEGF And PEDF

Diabetic retinopathy (DR) is the most common and most serious complications in the world today has become one of the four major blinding disease. In China, blinding as a result of DR has caused more than 70,000, the prevalence of diabetes with the extension of the duration of the increase. Patients with diabetes worldwide, prompted the increase in DR is still in the future vision loss and damage as the main reason.Studies have shown that chronic retinal neovascularization and retinal edema in diabetic retinopathy is a threat to the vision of two main reasons, and retinal neovascularization is the vitreous hemorrhage, retinal detachment, and ultimately the loss of vision in patients with the root causes. Retinal neovascularization and other parts of the body of the formation of new blood vessels the same, is a complex biological process. The study found hypoxic ischemic retinal neovascularization is the only dynamic factor in the clinical examination is often found that if the retinal capillary obliteration, the formation of large non-perfusion area, causing retinal ischemia, hypoxia, the corresponding region of retinal neovascularization easily, often Found in diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, and other diseases. On the surface, retinal neovascularization seems to compensate for the needs of the organization, but in fact play a role against the opposite. At present, the clinical use of laser photocoagulation and surgery, inhibit the development of retinal neovascularization, but we can not fundamentally solve the problem, the process of surgery at the same time there are likely to damage the retina, resulting in varying degrees of visual function damage, so the growth is inhibited angiogenesis The key to the treatment of this disease.In recent years, despite the large number of DR, effective research, but the specific mechanism is still not entirely clear, so the establishment of an appropriate animal model of diabetes has become to explore the incidence of diabetic retinopathy and to assess the mechanism of its drug treatment an important means. With the cell biology and molecular biology technology in-depth studies have shown that cytokines in the development of DR's role has been widespread concern and research. At present, more and more evidence that a variety of cytokines involved in angiogenesis regulation. Intraocular neovascularization may be due to the formation in a variety of cells and their secretion of cytokines in eye-control cell proliferation, and promoting the destruction of angiogenic factors and angiogenesis inhibitor balance between precision and eventually lead to normal tissue The growth of new blood vessels. Pathological state, led to an imbalance between the DR and development [21], new blood vessels inside the eye of prevention is to seek to restore this balance, or less antagonistic expression of angiogenic factors, or increase, stimulating blood vessel inhibitory factor Expression.VEGF is the most recognized of the endothelial cells selectively mitogenic and-angiogenic factors, specifically to stimulate the proliferation of endothelial cells involved in the formation of new blood vessels, and is considered to be DR neovascularization contact one of the most closely Factor. Pierce, and so on [18] Application of a proliferation of retinopathy rat model of VEGF found with retinal neovascularization in a marked increase in the expression, with their tips neovascularization of the retina play an important role.PEDF was first proposed by the Tombran-Tink from human fetal retinal pigment epithelial cell culture fluid conditioning in the separation and purification, has a neurotrophic effect. Dawson, and other [21,22] for the first time in 1999 found that PEDF also has a strong role in inhibiting blood vessel and at the same time, PEDF is considered to be the most effective natural inhibitor of angiogenesis, neovascularization in the PEDF inhibited the migration of endothelial cells [21 ]. Research also shows that, PEDF involved in the regulation of patients with PDR prior to the formation of retinal neovascularization [22]. The occurrence of blood vessels by stimulating blood vessel inhibitory factor and vascular-balance control. Normal tissues, blood vessel inhibitor take advantage of the impact, it will not happen angiogenesis, the pathological state, such as: PDR, tumors, blood vessels or to enhance stimulating factor / inhibitor reduced, leading to new blood vessels produce. VEGF and PEDF between a regulation against each other, PEDF can be greatly reduced vascular endothelial cells and retinal Muller cells of VEGF expression in the Muller cells with siRNA so that the sinking of the PEDF gene, can result in VEGF levels of mRNA and protein levels were significantly Increased PEDF is a description of the endogenous VEGF-negative regulator. Further significant studies have shown that not only can be induced by hypoxia VEGF promoter activity, can also be induced by hypoxia-inducible factor (HIF) nuclear translocation and mitogen-activated protein kinase (MAPK) phosphorylation, and over the course of PEDF may be inhibited . PEDF inhibited VEGF that took place in the level of transcription. And that in vitro, PEDF and VEGF could compete VEGFR-2, shows another mechanism of PEDF. On the other hand, VEGF significantly reduced the expression of PEDF. This speculation diabetic retinopathy in patients with partial expression of VEGF and PEDF, at least in part attributable to the reduction in the level, subsequently causing vascular leakage and neovascularization. Zhang [27], and other experiments have proved that as a major factor VEGF to stimulate blood vessels and potential blood vessel inhibitor PEDF on the balance between regulation of vascular leakage and the formation of new blood vessels essential.At present, there is no domestic scholars, including DR, the blood vessels in retinopathy morphology changes and changes in VEGF and PEDF at the same time, and only a few foreign countries also have had a rough literature reports, and in this regard DR Both have a level of relevance and its relationship with retinal neovascularization time and the extent of the dynamic relationship between the study did not report. Because the maintenance of normal eye steady since the formation of blood vessels by stimulating and inhibiting factors of these two decisions, so we speculated that in the case of pathological neovascularization in the mechanism of these two factors may also have some relevance In order to more objectively reflect the angiogenesis mechanism, so as to provide more treatment on the basis of value. At present, domestic and foreign scholars have not yet taken place on the DR mechanisms to stimulate angiogenesis factor VEGF and angiogenesis inhibitor PEDF between pathological significance and relevance of research carried out. To this end we have to be in the rat model of diabetes, based on morphological changes from the DR explore and produce VEGF and PEDF level of the relevance of the two, with the DR-time and the relationship between the degree of disease, prevention and early treatment of new DR Strategy.STZ using this experimental rat model of diabetic retinopathy with digestion-chip shop microvascular morphological change was observed by in situ hybridization and detection of PEDF mRNA in the rat model of 1, 3, 6 months in the retina of expression, and VEGF mRNA expression Comparison. The results showed that with the progress of the DR, to varying degrees of retinal blood vessels to change shape, such as tortuous Nuzhang capillaries, blood vessels and form a button loop knot, running irregularly; capillary lumen varying thickness, or the expansion of segments, was cystoid Expansion. With the extension of the duration of diabetes retinal capillary pericytes apparent reduction in the amount, with angiopoietin expression of VEGF mRNA increased inhibit angiogenesis PEDF mRNA expression, the dynamic balance between the two is broken, endothelial cells continued Hyperplasia, angiogenesis, the promotion of DR in particular the development of PDR.DR pathogenesis is the complex, our study found that VEGF and PEDF in DR expression level of change affecting the week Changes cells, leading to abnormal retinal capillaries, and the expression of VEGF mRNA and increased expression of PEDF mRNA reduce diabetic retinopathy and blood vessels The severity of the disease coincides with the development of DR existence of limitations of space and relations. Our results for a better understanding of the basic mechanisms of DR occurred, prevention and early treatment of DR provides new ideas. How to control the retina through the local expression of VEGF and PEDF to reduce the level of the retina or inhibit the formation of new blood vessels to be our further study.