Neurodegeneration and Neuroprotection in Diabetic Retinopathy

被引:77
作者
Ola, Mohammad Shamsul [1 ]
Nawaz, Mohd Imtiaz [1 ]
Khan, Haseeb A. [1 ]
Alhomida, Abdullah S. [1 ]
机构
[1] King Saud Univ, Dept Biochem, Fac Sci, Riyadh 11415, Saudi Arabia
关键词
diabetic retinopathy; drugs; neurodegeneration; retina; oxidative stress; glutamate; NEUROTROPHIC FACTOR BDNF; RETINAL GANGLION-CELLS; IN-VIVO; NEUROTRANSMITTER METABOLISM; HOMOCYSTEINE METABOLISM; GLUTAMATE METABOLISM; GLUCOSE-METABOLISM; GROWTH-FACTOR; MULLER CELLS; GLIAL-CELLS;
D O I
10.3390/ijms14022559
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2559 / 2572
页数:14
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