Regulation of retinal vascular permeability by betacellulin.
Regulation of retinal vascular permeability by betacellulin.
复制标题
β细胞素调节视网膜血管通透性。
DOI：
10.1007/978-1-4614-0631-0_38
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发表时间：
2012
影响因子：
--
通讯作者：
Anand-Apte,Bela
中科院分区：
文献类型：
--
作者：
Sugimoto,Masahiko;Cutler,Alecia;Grossman,Gregory;Anand-Apte,Bela
糖尿病性黄斑病变是2型糖尿病患者视力丧失的主要原因，其特征是视网膜血管渗透性过高，随后形成黄斑水肿和硬渗出物。流行病学研究表明，血糖控制在糖尿病血管并发症的发展中起主要作用（Diabetes 42：1555-1558，1993 b）。在一项干预队列研究中，糖尿病的强化治疗使增殖性糖尿病视网膜病变的发展减少了47%，但与严重低血糖的风险增加2 - 3倍（N Engl J Med 329：977-986，1993 a）和心血管死亡率相关。因此，关键是要确定一个下游血糖目标，有助于增加视网膜血管通透性，可以在治疗上有针对性，而没有与高血糖症的强化治疗相关的额外风险。β细胞素是表皮生长因子家族的32 kDa成员，除了胰岛的增殖β细胞之外，其还由视网膜色素上皮细胞和Muller细胞产生，并促进胰腺β细胞的再生（Growth Factors 13：181-191，1996; Endocrinol Metab 285：E577-583，2003; Diabetes 53：608-615，2004）。它对平滑肌细胞和视网膜色素上皮细胞的促有丝分裂活性使我们假设β细胞素在与糖尿病相关的视网膜血管并发症中的作用（Science 259：1604-1607，1993）。我们的研究（PLoS ONE 5：e13444，2010）表明糖尿病小鼠具有加重的视网膜血管通透性，伴随着视网膜中裂解的可溶形式的β细胞素（s-Btc）的表达增加。玻璃体内注射β-细胞素诱导正常血糖和高血糖小鼠视网膜出血和血管通透性增加。去整合素和金属蛋白酶ADAM-10（其在β细胞素的裂解中起作用）在糖尿病小鼠和患有糖尿病视网膜病变的人的视网膜中增加。基于这些结果，我们推测β细胞素可能有助于视网膜血管通透性增加和糖尿病黄斑水肿的发病机制。
Diabetic maculopathy, a leading cause of vision loss in patients with type 2 diabetes, is characterized by hyperpermeability of retinal blood vessels with subsequent formation of macular edema and hard exudates. Epidemiological studies have suggested that glycemic control plays a major role in the development of vascular complications of diabetes (Diabetes 42:1555–1558, 1993b). In an intervention cohort study, intensive treatment of diabetes reduced the development of proliferative diabetic retinopathy by 47% but was associated with a two to threefold increased risk of severe hypoglycemia (N Engl J Med 329:977–986, 1993a) and cardiovascular mortality. Therefore, it is critical to identify a downstream glycemic target that contributes to increased retinal vascular permeability that could be targeted therapeutically without the additional risks associated with intensive treatment of the hyperglycemia. Betacellulin is a 32 kDa member of the epidermal growth factor family that is produced by retinal pigment epithelial cells and Muller cells in addition to the proliferating β cells of the pancreatic islets and promotes regeneration of pancreatic β cells (Growth Factors 13:181–191, 1996; Endocrinol Metab 285:E577–583, 2003; Diabetes 53:608–615, 2004). Its mitogenic activity for smooth muscle cells and retinal pigment epithelial cells led us to hypothesize a role for betacellulin in the retinal vascular complications associated with diabetes (Science 259:1604–1607, 1993). Our studies (PLoS ONE 5:e13444, 2010) suggest that diabetic mice have accentuated retinal vascular permeability with a concomitant increased expression of a cleaved soluble form of betacellulin (s-Btc) in the retina. Intravitreal injection of betacellulin induced retinal hemorrhage and increased vascular permeability in normoglycemic and hyperglycemic mice. A disintegrin and metalloproteinase, ADAM-10 (which plays a role in the cleavage of betacellulin), is increased in the retinae of diabetic mice and humans with diabetic retinopathy. Based on these results, we hypothesize that betacellulin may contribute to increased retinal vascular permeability and the pathogenesis of diabetic macular edema.
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影响因子：
2
作者：
Miyagawa, J;Hanafusa, T;Matsuzawa, Y
通讯作者：
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