Neurodegeneration and neuroprotection in diabetic retinopathy.
Neurodegeneration and neuroprotection in diabetic retinopathy.
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DOI：
10.3390/ijms14022559
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发表时间：
2013-01-28
影响因子：
5.6
通讯作者：
Alhomida AS
中科院分区：
文献类型：
--
作者：
Ola MS;Nawaz MI;Khan HA;Alhomida AS
糖尿病视网膜病变被广泛认为是一种神经血管疾病。这与其先前仅作为血管疾病的身份形成对比。在糖尿病疾病进展的早期，视网膜神经元成分中的主要细胞由视网膜神经节细胞和神经胶质细胞组成，已经发现这两者都受到损害。许多视网膜功能测试也表明糖尿病视网膜的功能缺陷，这进一步支持神经元细胞的功能障碍。作为一种内分泌疾病，糖尿病改变了包括视网膜在内的几个身体器官的全身和局部代谢。越来越多的证据表明，糖尿病视网膜病变的情况下，兴奋毒性代谢物，包括谷氨酸，支链氨基酸和同型半胱氨酸的水平增加。此外，在疾病早期，叶酸和维生素B12水平降低，这是能够损害神经元的潜在代谢物。发现这些代谢物水平的改变激活了几种代谢途径，导致氧化应激增加和神经营养因子水平降低。因此，它们可能会损害糖尿病患者的视网膜神经元。本文就这些潜在的兴奋毒性代谢物及其在神经元损伤中的作用进行综述。还讨论了保护神经元的可能的治疗靶点。然而，需要进一步的研究来了解神经退行性变的确切分子机制，以便开发有效的神经保护策略。通过在糖尿病视网膜病变病例的早期保护视网膜神经元，可以保护视网膜血管的损伤，从而有助于改善糖尿病视网膜病变的进展，糖尿病视网膜病变是全球失明的主要原因。
Diabetic retinopathy is widely considered to be a neurovascular disease. This is in contrast to its previous identity as solely a vascular disease. Early in the disease progression of diabetes, the major cells in the neuronal component of the retina consist of retinal ganglion cells and glial cells, both of which have been found to be compromised. A number of retinal function tests also indicated a functional deficit in diabetic retina, which further supports dysfunction of neuronal cells. As an endocrinological disorder, diabetes alters metabolism both systemically and locally in several body organs, including the retina. A growing body of evidences indicates increased levels of excitotoxic metabolites, including glutamate, branched chain amino acids and homocysteine in cases of diabetic retinopathy. Also present, early in the disease, are decreased levels of folic acid and vitamin-B12, which are potential metabolites capable of damaging neurons. These altered levels of metabolites are found to activate several metabolic pathways, leading to increases in oxidative stress and decreases in the level of neurotrophic factors. As a consequence, they may damage retinal neurons in diabetic patients. In this review, we have discussed those potential excitotoxic metabolites and their implications in neuronal damage. Possible therapeutic targets to protect neurons are also discussed. However, further research is needed to understand the exact molecular mechanism of neurodegeneration so that effective neuroprotection strategies can be developed. By protecting retinal neurons early in diabetic retinopathy cases, damage of retinal vessels can be protected, thereby helping to ameliorate the progression of diabetic retinopathy, a leading cause of blindness worldwide.
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