Approaches to Potentiated Neuroprotective Treatment in the Rodent Model of Ischemic Optic Neuropathy

Nonarthritic anterior ischemic optic neuropathy (NAION) commonly causes sudden optic nerve (ON)-related vision loss. The rodent NAION model (rAION) closely resembles NAION in presentation and physiological responses. Researchers hypothesized that blocking pro-inflammatory prostaglandin (PGE2) production by inhibiting monoacylglycerol lipase or cyclooxygenase activity and co-administering PGJ2 would potentiate RGC survival following ischemic neuropathy. This study identified early rAION-associated optic nerve head (ONH) inflammatory gene expression responses and the anti-inflammatory prostaglandin PGJ2’s effects on those responses. Deep sequencing was performed on vehicle- and PGJ2-treated ONHs 3d post-rAION induction. Results were compared against responses from a retinal ischemia model. Animals were treated with PGJ2 and MAGL inhibitor KML29, or PGJ2 + COX inhibitor meloxicam. RGC survival was quantified by stereology.

非动脉炎性前缺血性视神经病变（NAION）常导致突然发生的视神经（ON）相关视力丧失。鼠类NAION模型（rAION）在表现和生理反应方面与NAION极为相似。研究人员假设，通过抑制单酰甘油脂酶或环氧合酶活性来阻断促炎性前列腺素（PGE2）的产生，并联合给予PGJ2，可以增强缺血性神经病变后视网膜神经节细胞（RGC）的存活。本研究确定了早期rAION相关视神经乳头（ONH）炎症基因表达反应，以及抗炎前列腺素PGJ2对这些反应的影响。在rAION诱导后3天对车辆处理组和PGJ2处理组的ONH进行了深度测序。结果与视网膜缺血模型中的反应进行了比较。动物接受了PGJ2和MAGL抑制剂KML29，或PGJ2加COX抑制剂美洛昔康的治疗。通过立体学方法量化了RGC的存活。