Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, Miami, FL 33136, USA.
Int J Mol Sci. 2018 Jan 13;19(1):237. doi: 10.3390/ijms19010237.
Blindness in glaucoma is the result of death of Retinal Ganglion Cells (RGCs) and their axons. RGC death is generally preceded by a stage of reversible dysfunction and structural remodeling. Current treatments aimed at reducing intraocular pressure (IOP) are ineffective or incompletely effective in management of the disease. IOP-independent neuroprotection or neuroprotection as adjuvant to IOP lowering in glaucoma remains a challenge as effective agents without side effects have not been identified yet. We show in DBA/2J mice with spontaneous IOP elevation and glaucoma that the lifespan of functional RGCs can be extended by preconditioning RGCs with retrobulbar lidocaine in one eye at four months of age that temporary blocks RGC axonal transport. The contralateral, PBS-injected eye served as control. Lidocaine-induced impairment of axonal transport to superior colliculi was assessed by intravitreal injection of cholera toxin B. Long-term (nine months) effect of lidocaine were assessed on RGC electrical responsiveness (PERG), IOP, expression of relevant protein (BDNF, TrkB, PSD95, GFAP, Synaptophysin, and GAPDH) and RGC density. While lidocaine treatment did not alter the age-related increase of IOP, TrkB expression was elevated, GFAP expression was decreased, RGC survival was improved by 35%, and PERG function was preserved. Results suggest that the lifespan of functional RGCs in mouse glaucoma can be extended by preconditioning RGCs in early stages of the disease using a minimally invasive treatment with retrobulbar lidocaine, a common ophthalmologic procedure. Lidocaine is inexpensive, safe and is approved by Food and Drug Administration (FDA) to be administered intravenously.
青光眼导致的失明是视网膜神经节细胞（RGC）及其轴突死亡的结果。RGC 死亡通常先于可逆性功能障碍和结构重塑阶段。目前旨在降低眼内压（IOP）的治疗方法在该疾病的治疗中无效或不完全有效。在青光眼患者中，减少 IOP 的神经保护或神经保护作为辅助治疗仍然是一个挑战，因为尚未确定有效且无副作用的药物。我们在 DBA/2J 小鼠中显示，在四个月大时用眶后利多卡因预处理一只眼，可以延长功能性 RGC 的寿命，该预处理暂时阻断了 RGC 轴突运输。对侧用 PBS 注射的眼睛作为对照。通过在眼内注射霍乱毒素 B 评估利多卡因对轴突运输到上丘的损伤。用利多卡因进行的长期（九个月）作用评估包括 RGC 电反应性（PERG）、IOP、相关蛋白（BDNF、TrkB、PSD95、GFAP、Synaptophysin 和 GAPDH）和 RGC 密度。虽然利多卡因治疗并未改变与年龄相关的 IOP 升高，但 TrkB 表达增加，GFAP 表达减少，RGC 存活率提高了 35%，PERG 功能得以保留。结果表明，在疾病的早期阶段，通过眶后利多卡因这种微创治疗预处理 RGC，可以延长患有青光眼的小鼠功能性 RGC 的寿命。利多卡因价格低廉、安全，且已获得美国食品和药物管理局（FDA）批准可静脉内给药。
