Maciulaitiene Ruta, Kalesnykas Giedrius, Pauza Dainius Haroldas, Januleviciene Ingrida
Department of Ophthalmology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Experimentica Ltd., Kuopio, Finland.
PLoS One. 2024 Aug 8;19(8):e0308671. doi: 10.1371/journal.pone.0308671. eCollection 2024.
Glaucoma is a multifactorial optic neuropathy that primarily affecting retinal ganglion cells (RGC). Brimonidine is an intraocular pressure-lowering drug with reported neuroprotective properties. This study aimed to compare the neuroprotective effects of topical and intraperitoneal (IP) brimonidine on RGCs from different retinal segments in a murine optic nerve crush (ONC) model.
forty-one Balb/c mice underwent unilateral ONC and were divided into three study groups: fifteen animals received saline drops twice per day and two additional IP injections of saline; fourteen mice received brimonidine drops twice per day; and 12 mice received brimonidine eye drops twice per day and two additional IP brimonidine injections. Animals were sacrificed seven days post-ONC, and immunohistochemical staining of retinal whole mounts was performed using neuronal NeuN and GFAP staining. Microscopic pictures of the central, middle, and peripheral regions of the retina were taken. The density of the retinal cells was assessed.
The total RGC density after ONC and RGC densities in all retinal eccentricities were significantly higher in the brimonidine eye drop and IP combination treatment group than in the saline drop + saline IP, and brimonidine drop treatment groups.
brimonidine eye drops supplemented with IP brimonidine injections improved RGC survival in a preclinical model of ONC.
青光眼是一种多因素性视神经病变,主要影响视网膜神经节细胞(RGC)。溴莫尼定是一种具有神经保护特性报道的降眼压药物。本研究旨在比较在小鼠视神经挤压(ONC)模型中,局部和腹腔内(IP)注射溴莫尼定对不同视网膜节段RGC的神经保护作用。
41只Balb/c小鼠接受单侧ONC,并分为三个研究组:15只动物每天接受两次生理盐水滴眼以及另外两次腹腔注射生理盐水;14只小鼠每天接受两次溴莫尼定滴眼;12只小鼠每天接受两次溴莫尼定滴眼以及另外两次腹腔注射溴莫尼定。在ONC后7天处死动物,并使用神经元NeuN和GFAP染色对视网膜全层进行免疫组织化学染色。拍摄视网膜中央、中间和周边区域的显微镜照片。评估视网膜细胞的密度。
在溴莫尼定滴眼和IP联合治疗组中,ONC后的总RGC密度以及所有视网膜离心度下的RGC密度均显著高于生理盐水滴眼+生理盐水IP组和溴莫尼定滴眼治疗组。
在ONC的临床前模型中,补充腹腔注射溴莫尼定的溴莫尼定滴眼改善了RGC的存活。