The Role of Inflammation in Diabetic Retinopathy.
The Role of Inflammation in Diabetic Retinopathy.
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DOI：
10.3389/fimmu.2020.583687
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发表时间：
2020
影响因子：
7.3
通讯作者：
Delibegovic M
中科院分区：
文献类型：
--
作者：
Forrester JV;Kuffova L;Delibegovic M
炎症是糖尿病和代谢综合征致病过程的核心，特别是在并发症的发生中涉及先天免疫。炎症是 1 型糖尿病的主要事件，其中感染（病毒）和/或自身免疫过程引发疾病；相比之下，慢性炎症是 2 型糖尿病的典型症状，被认为是胰岛素抵抗增加和葡萄糖代谢紊乱的后遗症。糖尿病视网膜病变（DR）被认为是一种血管和神经退行性疾病，是在糖尿病控制不佳多年后发生的。然而，DR 的许多临床特征都是晚期事件，反映了视网膜结构及其细胞组成的性质。事实上，视网膜微血管疾病是一种早期发病机制，由低度、持续的白细胞活化引起，导致毛细血管闭塞反复发作和进行性、磨损性视网膜缺血。后来出现的明显的 DR 临床症状是视网膜缺血的结果。涉及脂质和葡萄糖代谢的代谢失调可能导致白细胞活化。在分子水平上，我们已经证明巨噬细胞限制性蛋白酪氨酸磷酸酶 1B (PTP1B) 是涉及胰岛素抵抗的代谢综合征中炎症的关键调节因子，并且 PTP1B 失调可能是视网膜微血管疾病的基础。我们还表明，粘附的 CCR5+CD11b+ 单核巨噬细胞似乎选择性地参与视网膜微血管闭塞。在这篇综述中，我们讨论了早期白细胞激活与 DR 后期特征之间的关系、糖尿病微血管疾病和其他血管性视网膜病变之间的常见发病过程、高血糖和血脂异常诱导白细胞激活的机制、糖尿病微血管疾病涉及的信号机制以及可能预防这些视网膜病变的可能干预措施。我们还探讨了适应性免疫在 DR 中的可能作用。尽管玻璃体内抗 VEGF 治疗已显着改善 DR 的治疗，但仍有相当大比例的患者，特别是患有威胁视力的黄斑水肿的患者，未能做出反应。针对炎症过程的替代疗法可能具有优势。
Inflammation is central to pathogenic processes in diabetes mellitus and the metabolic syndrome and particularly implicates innate immunity in the development of complications. Inflammation is a primary event in Type 1 diabetes where infectious (viral) and/or autoimmune processes initiate disease; in contrast, chronic inflammation is typical in Type 2 diabetes and is considered a sequel to increasing insulin resistance and disturbed glucose metabolism. Diabetic retinopathy (DR) is perceived as a vascular and neurodegenerative disease which occurs after some years of poorly controlled diabetes. However, many of the clinical features of DR are late events and reflect the nature of the retinal architecture and its cellular composition. Retinal microvascular disease is, in fact, an early event pathogenetically, induced by low grade, persistent leukocyte activation which causes repeated episodes of capillary occlusion and, progressive, attritional retinal ischemia. The later, overt clinical signs of DR are a consequence of the retinal ischemia. Metabolic dysregulation involving both lipid and glucose metabolism may lead to leukocyte activation. On a molecular level, we have shown that macrophage-restricted protein tyrosine phosphatase 1B (PTP1B) is a key regulator of inflammation in the metabolic syndrome involving insulin resistance and it is possible that PTP1B dysregulation may underlie retinal microvascular disease. We have also shown that adherent CCR5+CD11b+ monocyte macrophages appear to be selectively involved in retinal microvascular occlusion. In this review, we discuss the relationship between early leukocyte activation and the later features of DR, common pathogenetic processes between diabetic microvascular disease and other vascular retinopathies, the mechanisms whereby leukocyte activation is induced in hyperglycemia and dyslipidemia, the signaling mechanisms involved in diabetic microvascular disease, and possible interventions which may prevent these retinopathies. We also address a possible role for adaptive immunity in DR. Although significant improvements in treatment of DR have been made with intravitreal anti-VEGF therapy, a sizeable proportion of patients, particularly with sight-threatening macular edema, fail to respond. Alternative therapies targeting inflammatory processes may offer an advantage.
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影响因子：
5.3
作者：
Al-Sharea A;Murphy AJ;Huggins LA;Hu Y;Goldberg IJ;Nagareddy PR
通讯作者：
Nagareddy PR
DOI：
10.33594/000000117
发表时间：
2019-01-01
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Akhter, Nadeem;Madhoun, Ashraf;Sindhu, Sardar
通讯作者：
Sindhu, Sardar
DOI：
10.1042/bj20110373
发表时间：
2011-09-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Agouni A;Mody N;Owen C;Czopek A;Zimmer D;Bentires-Alj M;Bence KK;Delibegović M
通讯作者：
Delibegović M
2型糖尿病 - 未满足的需求，未解决的发病机理，以MTORC1为中心的范例。
影响因子：
8.2
作者：
Bar-Tana J
通讯作者：
Bar-Tana J
影响因子：
1.8
作者：
Bhatwadekar AD;Duan Y;Korah M;Thinschmidt JS;Hu P;Leley SP;Caballero S;Shaw L;Busik J;Grant MB
通讯作者：
Grant MB