Deficient deposition of new myelin impairs adult optic nerve function in a murine model of diabetes

作者全名："Wu, Haoqian; Chen, Xianjun; Yu, Bin; Zhang, Jieqiong; Gu, Xingmei; Liu, Wei; Mei, Feng; Ye, Jian; Xiao, Lan"

作者地址："[Wu, Haoqian; Zhang, Jieqiong; Liu, Wei; Ye, Jian] Army Med Univ, Daping Hosp, Army Med Ctr, Dept Ophthalmol, 10 Changjiang Branch, Chongqing 400042, Peoples R China; [Chen, Xianjun] Chongqing Med Univ, Coll Basic Med Sci, Res Ctr Neurosci, Dept Physiol, Chongqing, Peoples R China; [Yu, Bin; Xiao, Lan] Army Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China; [Mei, Feng; Xiao, Lan] Army Med Univ, Dept Histol & Embryol, Brain & Intelligence Res Key Lab Chongqing Educ Co, Chongqing 400038, Peoples R China"

通信作者："Ye, J (通讯作者)，Army Med Univ, Daping Hosp, Army Med Ctr, Dept Ophthalmol, 10 Changjiang Branch, Chongqing 400042, Peoples R China.; Mei, F; Xiao, L (通讯作者)，Army Med Univ, Dept Histol & Embryol, Brain & Intelligence Res Key Lab Chongqing Educ Co, Chongqing 400038, Peoples R China."

来源：GLIA

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000916010200001

JCR分区：Q1

影响因子：5.4

年份：2023

卷号：71

期号：5

开始页：1333

结束页：1345

文献类型：Article

关键词：clemastine; diabetes mellitus; myelination; optic nerve; oligodendroglia

摘要："Visual impairment in diabetes is a growing public health concern. Apart from the well-defined diabetic retinopathy, disturbed optic nerve function, which is dependent on the myelin sheath, has recently been recognized as an early feature of visual impairment in diabetes. However, the underlying cellular mechanisms remain unclear. Using a streptozotocin-induced diabetic mouse model, we observed a myelin deficiency along with a disturbed composition of oligodendroglial lineage cells in diabetic optic nerve. We found that new myelin deposition, a continuous process that lasts throughout adulthood, was diminished during pathogenesis. Genetically dampening newly generated myelin by conditionally deleting olig2 in oligodendrocyte precursor cells within this short time window extensively delayed the signal transmission of the adult optic nerve. In addition, clemastine, an antimuscarinic compound that enhances myelination, significantly restored oligodendroglia, and promoted the functional recovery of the optic nerve in diabetic mice. Together, our results point to the role of new myelin deposition in optic neuropathy under diabetic insult and provide a promising therapeutic target for restoring visual function."

基金机构："STI [2021ZD0201700]; National Natural Science Foundation of China [32000684, 31921003]; Chongqing Natural Science Foundation [cstc2021jcyj-msxmX0164, CSTB2022BSXM-JCX0056]"

基金资助正文："STI 2030-Major Projects, Grant/AwardNumber: 2021ZD0201700; National NaturalScience Foundation of China, Grant/AwardNumbers: 32000684, 31921003; ChongqingNatural Science Foundation, Grant/AwardNumbers: CSTB2022BSXM-JCX0056,cstc2021jcyj-msxmX0164"