Proteomic Analysis of Early Diabetic Retinopathy Reveals Mediators of Neurodegenerative Brain Diseases

Investigative Ophthalmology & Visual Science
Jeffrey M SundstromR Simó

Abstract

Current evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy. Our main goal was to examine whether, in the diabetic human retina, common proteins and pathways are shared with brain neurodegenerative diseases. A proteomic analysis was performed on three groups of postmortem retinas matched by age: nondiabetic control retinas (n = 5), diabetic retinas without glial activation (n = 5), and diabetic retinas with glial activation (n = 5). Retinal lysates from each group were pooled and run on an SDS-PAGE gel. Bands were analyzed sequentially by liquid chromatography-mass spectrometry (LC/MS) using an Orbitrap Mass Spectrometer. A total of 2190 proteins were identified across all groups. To evaluate the association of the identified proteins with neurological signaling, significant signaling pathways belonging to the category "Neurotransmitters and Other Nervous System Signaling" were selected for analysis. Pathway analysis revealed that "Neuroprotective Role of THOP1 in Alzheimer's Disease" and "Unfolded Protein Response" pathways were uniquely enriched in control retinas. By contrast, "Dopamine Degradation" and "Parkinson's Signaling" were enriched only in diabetic retinas w...Continue Reading

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Citations

Jan 10, 2019·Current Eye Research·Mustafa IftikharRoomasa Channa
Jan 11, 2019·Journal of Clinical Medicine·Olga Simó-ServatRafael Simó
May 6, 2019·Current Eye Research·Fiona CunninghamAlan W Stitt
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Oct 15, 2019·Frontiers in Neuroscience·Sapana SharmaVasudharani Devanathan
Jun 2, 2020·The Journal of Biological Chemistry·Sadie K DierschkeMichael D Dennis
Jul 10, 2019·Current Eye Research·Sachin ShuklaSayan Basu
Jun 20, 2020·Diabetologia·Rafael SimóAngelo Avogaro
Aug 9, 2020·Eye and Brain·Georgios TsokolasStraton Tyradellis
Jun 28, 2019·Journal of Clinical Medicine·Todd McLaughlinSarah X Zhang
Dec 31, 2020·The Journal of Clinical Endocrinology and Metabolism·Ward FickweilerGeorge L King
Jan 12, 2021·Progress in Retinal and Eye Research·Warren W PanPatrice E Fort
Jan 21, 2021·Nature Reviews. Endocrinology·David A AntonettiAlan W Stitt
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Apr 4, 2021·Journal of Clinical Medicine·Warren W PanJennifer L Harder
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Aug 29, 2021·Pharmaceutics·Rafael SimóCristina Hernández
Dec 7, 2021·Frontiers in Cell and Developmental Biology·Türküler ÖzgümüsValeriya Lyssenko

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Software Mentioned

Olimpus Fluoview
Sequest
Proteome Discoverer
Scaffold
IPA

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