Proteomic Analysis of Early Diabetic Retinopathy RevealsMediators of Neurodegenerative Brain Diseases

Investigative Ophthalmology & Visual Science

article

Jeffrey M. Sundstrom¹  Cristina Hernández²  Sarah R. Weber¹  Yuanjun Zhao¹  Mitchell Dunklebarger¹  Natalia Tiberti⁴  Tatiana Laremore⁵  Olga Simó-Servat²  Marta Garcia-Ramirez²  Alistair J. Barber¹  Thomas W. Gardner⁶  Rafael Simó² 

[1] Penn State Hershey Eye Center, Penn State College of Medicine;Institut de Recerca Hospital Universitari Vall d"Hebron;Instituto de Salud Carlos III;University of Technology;Proteomics and Mass Spectrometry Core Facility, Penn State University;Kellogg Eye Center, University of Michigan Medical School

关键词: proteomics;    diabetic retinopathy;    human;    neurodegeneration;    retina;   

DOI  :  10.1167/iovs.17-23678

学科分类：社会科学、人文和艺术（综合）

来源: Association for Research in Vision and Ophthalmology

【 摘 要 】

PURPOSE. Current evidence suggests that retinal neurodegeneration is an early event in thepathogenesis of diabetic retinopathy. Our main goal was to examine whether, in the diabetichuman retina, common proteins and pathways are shared with brain neurodegenerativediseases.METHODS. A proteomic analysis was performed on three groups of postmortem retinasmatched by age: nondiabetic control retinas (n ¼ 5), diabetic retinas without glial activation(n ¼ 5), and diabetic retinas with glial activation (n ¼ 5). Retinal lysates from each groupwere pooled and run on an SDS-PAGE gel. Bands were analyzed sequentially by liquidchromatography-mass spectrometry (LC/MS) using an Orbitrap Mass Spectrometer.RESULTS. A total of 2190 proteins were identified across all groups. To evaluate the associationof the identified proteins with neurological signaling, significant signaling pathways belongingto the category ‘‘Neurotransmitters and Other Nervous System Signaling’’ were selected foranalysis. Pathway analysis revealed that ‘‘Neuroprotective Role of THOP1 in Alzheimer’sDisease’’ and ‘‘Unfolded Protein Response’’ pathways were uniquely enriched in controlretinas. By contrast, ‘‘Dopamine Degradation’’ and ‘‘Parkinson’s Signaling’’ were enrichedonly in diabetic retinas with glial activation. The ‘‘Neuregulin Signaling,’’ ‘‘Synaptic Long TermPotentiation,’’ and ‘‘Amyloid Processing’’ pathways were enriched in diabetic retinas with noglial activation.CONCLUSIONS. Diabetes-induced retinal neurodegeneration and brain neurodegenerativediseases, such as Alzheimer’s and Parkinson’s diseases, share common pathogenic pathways.These findings suggest that the study of neurodegeneration in the diabetic retina could beuseful to further understand the neurodegenerative processes that occur in the brain ofpersons with diabetes.

【 授权许可】

CC BY|CC BY-NC-ND