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Abstract：
BACKGROUND: Vascular dysregulation is one of the major risk factors of glaucoma, and endothelin-1 (ET-1) may have a role in the pathogenesis of vascular-related glaucoma. Fruit extract from Lycium Barbarum (LB) exhibits anti-ageing and multitarget mechanisms in protecting retinal ganglion cells (RGC) in various animal models. To investigate the therapeutic efficacy of LB glycoproteins (LbGP) in ET-1 induced RGC degeneration, LbGP was applied under pre- and posttreatment conditions to an ET-1 mouse model. Retina structural and functional outcomes were characterised using clinical-based techniques.
METHODS: Adult C57BL/6 mice were randomly allocated into four experimental groups, namely vehicle control (n = 9), LbGP-Pretreatment (n = 8), LbGP-Posttreatment (day 1) (n = 8) and LbGP-Posttreatment (day 5) (n = 7). Oral administration of LbGP 1 mg/Kg or PBS for vehicle control was given once daily. Pre- and posttreatment (day 1 or 5) were commenced at 1 week before and 1 or 5 days after intravitreal injections, respectively, and were continued until postinjection day 28. Effects of treatment on retinal structure and functions were evaluated using optical coherence tomography (OCT), doppler OCT and electroretinogram measurements at baseline, post-injection days 10 and 28. RGC survival was evaluated by using RBPMS immunostaining on retinal wholemounts.
RESULTS: ET-1 injection in vehicle control induced transient reductions in arterial flow and retinal functions, leading to significant RNFL thinning and RGC loss at day 28. Although ET-1 induced a transient loss in blood flow or retinal functions in all LbGP groups, LbGP treatments facilitated better restoration of retinal flow and retinal functions as compared with the vehicle control. Also, all three LbGP treatment groups (i.e. pre- and posttreatments from days 1 or 5) significantly preserved thRNFL thickness and RGC densities. No significant difference in protective effects was observed among the three LbGP treatment groups.
CONCLUSIONS: LbGP demonstrated neuroprotective effects in a mouse model of ET-1 induced RGC degeneration, with treatment applied either as a pretreatment, immediate or delayed posttreatment. LbGP treatment promoted a better restoration of retinal blood flow, and protected the RNFL, RGC density and retinal functions. This study showed the translational potential of LB as complementary treatment for glaucoma management.
METHODS: Adult C57BL/6 mice were randomly allocated into four experimental groups, namely vehicle control (n = 9), LbGP-Pretreatment (n = 8), LbGP-Posttreatment (day 1) (n = 8) and LbGP-Posttreatment (day 5) (n = 7). Oral administration of LbGP 1 mg/Kg or PBS for vehicle control was given once daily. Pre- and posttreatment (day 1 or 5) were commenced at 1 week before and 1 or 5 days after intravitreal injections, respectively, and were continued until postinjection day 28. Effects of treatment on retinal structure and functions were evaluated using optical coherence tomography (OCT), doppler OCT and electroretinogram measurements at baseline, post-injection days 10 and 28. RGC survival was evaluated by using RBPMS immunostaining on retinal wholemounts.
RESULTS: ET-1 injection in vehicle control induced transient reductions in arterial flow and retinal functions, leading to significant RNFL thinning and RGC loss at day 28. Although ET-1 induced a transient loss in blood flow or retinal functions in all LbGP groups, LbGP treatments facilitated better restoration of retinal flow and retinal functions as compared with the vehicle control. Also, all three LbGP treatment groups (i.e. pre- and posttreatments from days 1 or 5) significantly preserved thRNFL thickness and RGC densities. No significant difference in protective effects was observed among the three LbGP treatment groups.
CONCLUSIONS: LbGP demonstrated neuroprotective effects in a mouse model of ET-1 induced RGC degeneration, with treatment applied either as a pretreatment, immediate or delayed posttreatment. LbGP treatment promoted a better restoration of retinal blood flow, and protected the RNFL, RGC density and retinal functions. This study showed the translational potential of LB as complementary treatment for glaucoma management.
摘要：
背景：血管失调是青光眼的主要危险因素之一，内皮素-1（ET-1）可能在血管性青光眼的发病机制中起作用。枸杞果实提取物（LB）在各种动物模型中表现出抗衰老和保护视网膜神经节细胞（RGC）的多靶点机制。探讨LB糖蛋白(LbGP)在ET-1诱导的RGC变性中的疗效,在预处理和后处理条件下将LbGP应用于ET-1小鼠模型。使用基于临床的技术表征视网膜结构和功能结果。
方法：将成年C57BL/6小鼠随机分为四个实验组，即车辆控制(n=9)，LbGP预处理（n=8），LbGP-后处理(第1天)(n=8)和LbGP-后处理(第5天)(n=7)。每天一次口服施用lmg/Kg的LbGP或用于载体对照的PBS。治疗前和治疗后（第1天或第5天）在玻璃体内注射前1周和后1或5天开始，分别,并持续到注射后第28天。使用光学相干断层扫描（OCT）评估治疗对视网膜结构和功能的影响，基线时多普勒OCT和视网膜电图测量,注射后第10天和第28天。通过在视网膜整体上使用RBPMS免疫染色来评估RGC存活。
结果：在媒介物对照中注射ET-1引起动脉流量和视网膜功能的短暂减少，在第28天导致显著的RNFL变薄和RGC损失。尽管在所有LbGP组中ET-1引起血流或视网膜功能的短暂丧失，与载体对照相比,LbGP治疗促进更好地恢复视网膜血流和视网膜功能。此外，所有三个LbGP治疗组(即从第1天或第5天的治疗前和治疗后)均显著保留了RNFL厚度和RGC密度。在三个LbGP治疗组之间没有观察到保护作用的显著差异。
结论：LbGP在ET-1诱导的RGC变性小鼠模型中显示出神经保护作用，将治疗作为预处理，立即或延迟后治疗。LbGP治疗促进了视网膜血流的更好恢复，并保护了RNFL，RGC密度和视网膜功能。这项研究显示了LB作为青光眼治疗的补充治疗的转化潜力。
方法：将成年C57BL/6小鼠随机分为四个实验组，即车辆控制(n=9)，LbGP预处理（n=8），LbGP-后处理(第1天)(n=8)和LbGP-后处理(第5天)(n=7)。每天一次口服施用lmg/Kg的LbGP或用于载体对照的PBS。治疗前和治疗后（第1天或第5天）在玻璃体内注射前1周和后1或5天开始，分别,并持续到注射后第28天。使用光学相干断层扫描（OCT）评估治疗对视网膜结构和功能的影响，基线时多普勒OCT和视网膜电图测量,注射后第10天和第28天。通过在视网膜整体上使用RBPMS免疫染色来评估RGC存活。
结果：在媒介物对照中注射ET-1引起动脉流量和视网膜功能的短暂减少，在第28天导致显著的RNFL变薄和RGC损失。尽管在所有LbGP组中ET-1引起血流或视网膜功能的短暂丧失，与载体对照相比,LbGP治疗促进更好地恢复视网膜血流和视网膜功能。此外，所有三个LbGP治疗组(即从第1天或第5天的治疗前和治疗后)均显著保留了RNFL厚度和RGC密度。在三个LbGP治疗组之间没有观察到保护作用的显著差异。
结论：LbGP在ET-1诱导的RGC变性小鼠模型中显示出神经保护作用，将治疗作为预处理，立即或延迟后治疗。LbGP治疗促进了视网膜血流的更好恢复，并保护了RNFL，RGC密度和视网膜功能。这项研究显示了LB作为青光眼治疗的补充治疗的转化潜力。
