Ocular manifestations of central insulin resistance  

作　　者：Muneeb A.Faiq Trina Sengupta Madhu Nath Thirumurthy Velpandian Daman Saluja Rima Dada Tanuj Dada Kevin C.Chan 

机构地区：[1]Dr.Rajendra Prasad Centre for Ophthalmic Sciences,All India Institute of Medical Sciences,New Delhi,India [2]Neuroimaging and Visual Science Laboratory,Department of Ophthalmology,NYU Grossman School of Medicine,NYU Langone Health,New York University,New York,NY,USA [3]Medical Biotechnology Laboratory,Dr.B.R.Ambedkar Center for Biomedical Research,University of Delhi,Delhi,India [4]Dr.Baldev Singh Sleep Laboratory,Department of Physiology,All India Institute of Medical Sciences,New Delhi,India [5]Department of Ocular Pharmacology,Dr.Rajendra Prasad Center for Ophthalmic Sciences,All India Institute of Medical Sciences,New Delhi,India [6]Laboratory for Molecular Reproduction and Genetics,Department of Anatomy,All India Institute of Medical Sciences,New Delhi,India

出　　处：《Neural Regeneration Research》2023年第5期1139-1146,共8页中国神经再生研究（英文版）

基　　金：supported by a grant from All India Institute of Medical Sciences,New Delhi (to RD and TD);Indian Council of Medical Research,Senior Research Fellowship Grant (3/1/2(24)/oph-2009-NCD-II,to MAF);Feldstein Medical Foundation Research Grant (to KCC);unrestricted fund from Research to Prevent Blindness to NYU Langone Health Department of Ophthalmology (to KCC)。

摘　　要：Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammat

关 键 词：brain ciliary bodies gene expression inflammation insulin receptor insulin resistance intraocular pressure NEURODEGENERATION optic nerve RETINA retinal ganglion cells trabecular meshwork 

分 类 号：R587[医药卫生—内分泌]