Shibeeb O'Sam, Chidlow Glyn, Han Guoge, Wood John P M, Casson Robert J
Ophthalmic Research Laboratories, South Australian Institute of Ophthalmology, Centre for Neurological Diseases, Hanson Institute, Adelaide, South Australia, Australia.
University of Adelaide, Adelaide, South Australia, Australia.
Clin Exp Ophthalmol. 2016 Jan-Feb;44(1):24-32. doi: 10.1111/ceo.12581. Epub 2015 Aug 12.
This study aims to evaluate the effect of subconjunctival glucose on the retinal ganglion cells (RGCs) in experimental retinal ischaemia and contrast sensitivity in humans with primary open-angle glaucoma (POAG).
First, we measured the intravitreal concentration of glucose at various time points after a subconjunctival injection of 100 μl of 50% glucose to Sprague-Dawley rats. Next, treatment and control groups received 50% subconjunctival glucose and iso-osmotic (8%) saline, respectively, 1 h prior to a unilateral ischaemic retinal injury; 7 days later, the damage profiles were compared using RGC and axon counts. Subsequently, we conducted a double-blind, crossover, pilot clinical study in seven eyes of five pseudophakic subjects with severe POAG. Subjects received either 0.3 mL of 50% glucose subconjunctivally or iso-osmotic (8%) saline, then vice versa after a 2-3 week 'wash-out' period; change in contrast sensitivity from baseline was the primary outcome.
Subconjunctival glucose preserved approximately 60% of Brn3a-positive RGCs in all retinal zones compared with an 80% loss in control retinas, and rescued approximately 40% of the axonal loss. In the human trial, the contrast sensitivity at 12 cycles/degree was 0.24 log units greater than baseline (95% confidence interval 0.12-0.36; P < 0.001).
Subconjunctival glucose partially protects RGC somata and axons against an ischaemic insult and temporarily recovers contrast sensitivity in patients with severe POAG. Although an unlikely therapeutic strategy for POAG, the findings motivate further bioenergetic-based research in glaucoma and other optic nerve and retinal diseases, where energy failure may be part of the pathogenesis.
本研究旨在评估结膜下注射葡萄糖对实验性视网膜缺血模型中视网膜神经节细胞（RGCs）的影响，以及对原发性开角型青光眼（POAG）患者对比敏感度的影响。
首先，向Sprague-Dawley大鼠结膜下注射100μl 50%葡萄糖，在不同时间点测量玻璃体内葡萄糖浓度。其次，治疗组和对照组在单侧缺血性视网膜损伤前1小时，分别接受50%结膜下葡萄糖和等渗（8%）盐水注射；7天后，通过RGC和轴突计数比较损伤情况。随后，我们对5例严重POAG的假晶状体受试者的7只眼进行了双盲、交叉、先导性临床研究。受试者结膜下注射0.3mL 50%葡萄糖或等渗（8%）盐水，2-3周“洗脱期”后交换；主要观察指标为对比敏感度相对于基线的变化。
与对照组视网膜80%的RGCs损失相比，结膜下注射葡萄糖使所有视网膜区域中约60%的Brn3a阳性RGCs得以保留，并挽救了约40%的轴突损失。在人体试验中，12周/度时的对比敏感度比基线高0.24对数单位（95%置信区间0.12-0.36；P<0.001）。
结膜下注射葡萄糖可部分保护RGCs的胞体和轴突免受缺血性损伤，并能暂时恢复严重POAG患者的对比敏感度。尽管这对POAG来说不太可能成为一种治疗策略，但这些发现促使人们在青光眼以及其他可能存在能量衰竭参与发病机制的视神经和视网膜疾病中，开展更多基于生物能量学的研究。
