Role of CAST-Drp1 Pathway in Retinal Neuron-Regulated Necrosis in Experimental Glaucoma  

作　　者：Su-mei LIU Lv-shuang LIAO Ju-fang HUANG Shu-chao WANG 

机构地区：[1]Department of Anesthesiology,The Second Xiangya Hospital of Central South University,Changsha,410011,China [2]Center for Medical Research,The Second Xiangya Hospital of Central South University,Changsha,410011,China [3]Department of Anatomy and Neurobiology,School of Basic Medical Sciences,Central South University,Changsha,410013,China [4]School of Physical Education,Hunan Institute of Science and Technology,Yueyang,430600,China

出　　处：《Current Medical Science》2023年第1期166-172,共7页当代医学科学（英文）

基　　金：supported by the National Natural Science Foundation of China(No.82101126);the Natural Science Foundation of Hunan Province(No.2021JJ40873).

摘　　要：Objective Numerous studies have indicated that excitatory amino acid toxicity,such as glutamate toxicity,is involved in glaucoma.In addition,excessive glutamate can lead to an intracellular calcium overload,resulting in regulated necrosis.Our previous studies have found that the calpastatin(CAST)-calpain pathway plays an important role in retinal neuron-regulated necrosis after glutamate injury.Although inhibition of the calpain pathway can decrease regulated necrosis,necrotic cells remain.It has been suggested that there are other molecules that participate in retinal neuron-regulated necrosis.CAST is an important regulator of dynamin-related protein 1(Drp1)-mediated mitochondrial defects.Thus,the aim of this study was to determine whether the CAST-Drp1 pathway may be an underlying signaling axis in neuron-regulated necrosis.Methods Using cultured retinal neurons and in an in-vivo glaucoma model induced by glutamate overload,members of the CAST-Drp1 pathway were assessed by immunofluorescence,Western blotting,Phos-tagTM SDS-PAGE,and co-immunoprecipitation assays.Moreover,the black and white box test was performed on the rats.Results We found that more retinal neuron-regulated necrosis and Drp1 activation as well as lower CAST levels were present in the glutamate-induced glaucoma model.Rats with glutamate-induced glaucoma exhibited impaired visual function.We also observed retinal neuron-regulated necrosis and Drp1 activity decreased,and impaired vision recovered after CAST active peptide application,indicating that the CAST-Drp1 pathway plays a critical role in retinal neuron-regulated necrosis and visual function.Conclusion The results of this study indicate that the CAST-Drp1 pathway protects against retinal neuron-regulated necrosis,which may expand the therapeutic targets for the treatment of neurodegenerative disorders involving dysfunction of glutamate metabolism,such as glaucoma.

关 键 词：retinal ganglion cells GLAUCOMA CALPASTATIN dynamin-related protein l central nervous system regulated necrosis GLUTAMATE 

分 类 号：R775.2[医药卫生—眼科]