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Therapeutic targeting of diabetic retinal neuropathy as a strategy in preventing diabetic retinopathy

机译:糖尿病视网膜神经病变的治疗靶向作为预防糖尿病性视网膜病变的策略

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摘要

Diabetes causes a panretinal neurodegeneration herein termed diabetic retinal neuropathy, which manifests in the retina early and progresses throughout the disease. Clinical manifestations include changes in the ERG, perimetry, dark adaptation, contrast sensitivity and colour vision which correlate with laboratory findings of thinning of the retinal neuronal layers, increased apoptosis in neurons and activation of glial cells. Possible mechanisms include oxidative stress, neuronal AGE accumulation, altered balance of neurotrophic factors and loss of mitohormesis. Retinal neural damage precedes and is a biologically plausible cause of retinal vasculopathy later in diabetes, and this review suggests that strategies to target it directly could prevent diabetes induced blindness. The efficacy of fenofibrate in reducing retinopathy progression provides a possible proof of concept for this approach. Strategies which may target diabetic retinal neuropathy include reducing retinal metabolic demand, improving mitochondrial function with AMPK and Sirt1 activators or providing neurotrophic support with neurotrophic supplementation.
机译:糖尿病引起本文称为糖尿病性视网膜神经病的全视网膜神经变性,其在视网膜中早期出现并在整个疾病中进展。临床表现包括ERG的改变,视野检查,暗适应,对比敏感度和色觉,这些与实验室发现的视网膜神经元层变薄,神经元凋亡增加和神经胶质细胞活化有关。可能的机制包括氧化应激,神经元AGE积累,神经营养因子平衡的改变和线粒体功能丧失。视网膜神经损伤先于糖尿病,并且在糖尿病后期是视网膜血管病变的生物学上合理的原因,而这项综述表明,直接针对其的策略可以预防糖尿病引起的失明。非诺贝特在减少视网膜病变进展中的功效为这种方法提供了可能的概念证明。可能针对糖尿病性视网膜神经病的策略包括减少视网膜代谢需求,使用AMPK和Sirt1激活剂改善线粒体功能或通过补充神经营养提供神经营养支持。

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