Feenstra Derrick J, Yego E Chepchumba, Mohr Susanne
Department of Physiology, Michigan State University, East Lansing, MI, USA.
Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving, Ground, MD, USA.
J Clin Exp Ophthalmol. 2013 Oct 1;4(5):298. doi: 10.4172/2155-9570.1000298.
Cell death seems to be a prominent feature in the progression of diabetic retinopathy. Several retinal cell types have been identified to undergo cell death in a diabetic environment. Most emphasis has been directed towards identifying apoptosis in the diabetic retina. However, new research has established that there are multiple forms of cell death. This review discusses the different modes of cell death and attempts to classify cell death of retinal cells known to die in diabetic retinopathy. Special emphasis is given to apoptosis, necrosis, autophagic cell death, and pyroptosis. It seems that different retinal cell types are dying by diverse types of cell death. Whereas endothelial cells predominantly undergo apoptosis, pericytes might die by apoptosis as well as necrosis. On the other hand, Müller cells are suggested to die by a pyroptotic mechanism. Diabetes leads to significant Müller cell loss at 7 months duration of diabetes in retinas of diabetic mice compared to non-diabetic, which is prevented by the inhibition of the caspase-1/IL-1β (interleukin-1beta) pathway using the IL-1 receptor knockout mouse. Since pyroptosis is characterized by the activation of the caspase-1/IL-1β pathway subsequently leading to cell death, Müller cells seem to be a prime candidate for this form of inflammation-driven cell death. Considering that diabetic retinopathy is now discussed to potentially be a chronic inflammatory disease, pyroptotic cell death might play an important role in disease progression. Understanding mechanisms of cell death will lead to a more targeted approach in the development of new therapies to treat diabetic retinopathy.
细胞死亡似乎是糖尿病视网膜病变进展过程中的一个显著特征。已确定几种视网膜细胞类型在糖尿病环境中会发生细胞死亡。大部分研究重点都放在了识别糖尿病视网膜中的细胞凋亡上。然而，新的研究表明存在多种形式的细胞死亡。本综述讨论了不同的细胞死亡模式，并试图对已知在糖尿病视网膜病变中死亡的视网膜细胞的细胞死亡进行分类。特别强调了细胞凋亡、坏死、自噬性细胞死亡和焦亡。似乎不同的视网膜细胞类型会通过不同类型的细胞死亡方式死亡。内皮细胞主要发生细胞凋亡，周细胞可能通过细胞凋亡和坏死两种方式死亡。另一方面，有研究表明 Müller 细胞通过焦亡机制死亡。与非糖尿病小鼠相比，糖尿病小鼠视网膜在糖尿病病程 7 个月时会导致显著的 Müller 细胞丢失，而使用白细胞介素 -1 受体敲除小鼠抑制半胱天冬酶 -1/白细胞介素 -1β 途径可预防这种情况。由于焦亡的特征是半胱天冬酶 -1/白细胞介素 -1β 途径的激活，随后导致细胞死亡，因此 Müller 细胞似乎是这种炎症驱动的细胞死亡形式的主要候选者。鉴于现在认为糖尿病视网膜病变可能是一种慢性炎症性疾病，焦亡性细胞死亡可能在疾病进展中起重要作用。了解细胞死亡机制将为开发治疗糖尿病视网膜病变的新疗法带来更有针对性的方法。
