Proteomic analysis of early diabetic retinopathy reveals mediators of neurodegenerative brain diseases

Jeffrey Sundstrom, Cristina Hernández, Sarah R. Weber, Yuanjun Zhao, Mitchell Dunklebarger, Natalia Tiberti, Tatiana Nikolaevna Laremore, Olga Simó-Servat, Marta Garcia-Ramirez, Alistair Barber, Thomas W. Gardner, Rafael Simó

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

PURPOSE. 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. METHODS. 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. RESULTS. 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 with glial activation. The ‘‘Neuregulin Signaling,” “Synaptic Long Term Potentiation,” and “Amyloid Processing” pathways were enriched in diabetic retinas with no glial activation. CONCLUSIONS. Diabetes-induced retinal neurodegeneration and brain neurodegenerative diseases, 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 be useful to further understand the neurodegenerative processes that occur in the brain of persons with diabetes.

Original languageEnglish (US)
Pages (from-to)2264-2274
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number6
DOIs
StatePublished - May 1 2018

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Brain Diseases
Diabetic Retinopathy
Neurodegenerative Diseases
Proteomics
Retina
Neuroglia
Alzheimer Disease
Neuregulins
Retinaldehyde
Unfolded Protein Response
Proteins
Long-Term Potentiation
Amyloid
Liquid Chromatography
Nervous System
Neurotransmitter Agents
Parkinson Disease
Polyacrylamide Gel Electrophoresis
Dopamine
Mass Spectrometry

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Sundstrom, Jeffrey ; Hernández, Cristina ; Weber, Sarah R. ; Zhao, Yuanjun ; Dunklebarger, Mitchell ; Tiberti, Natalia ; Laremore, Tatiana Nikolaevna ; Simó-Servat, Olga ; Garcia-Ramirez, Marta ; Barber, Alistair ; Gardner, Thomas W. ; Simó, Rafael. / Proteomic analysis of early diabetic retinopathy reveals mediators of neurodegenerative brain diseases. In: Investigative Ophthalmology and Visual Science. 2018 ; Vol. 59, No. 6. pp. 2264-2274.
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title = "Proteomic analysis of early diabetic retinopathy reveals mediators of neurodegenerative brain diseases",
abstract = "PURPOSE. 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. METHODS. 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. RESULTS. 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 with glial activation. The ‘‘Neuregulin Signaling,” “Synaptic Long Term Potentiation,” and “Amyloid Processing” pathways were enriched in diabetic retinas with no glial activation. CONCLUSIONS. Diabetes-induced retinal neurodegeneration and brain neurodegenerative diseases, 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 be useful to further understand the neurodegenerative processes that occur in the brain of persons with diabetes.",
author = "Jeffrey Sundstrom and Cristina Hern{\'a}ndez and Weber, {Sarah R.} and Yuanjun Zhao and Mitchell Dunklebarger and Natalia Tiberti and Laremore, {Tatiana Nikolaevna} and Olga Sim{\'o}-Servat and Marta Garcia-Ramirez and Alistair Barber and Gardner, {Thomas W.} and Rafael Sim{\'o}",
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Sundstrom, J, Hernández, C, Weber, SR, Zhao, Y, Dunklebarger, M, Tiberti, N, Laremore, TN, Simó-Servat, O, Garcia-Ramirez, M, Barber, A, Gardner, TW & Simó, R 2018, 'Proteomic analysis of early diabetic retinopathy reveals mediators of neurodegenerative brain diseases', Investigative Ophthalmology and Visual Science, vol. 59, no. 6, pp. 2264-2274. https://doi.org/10.1167/iovs.17-23678

Proteomic analysis of early diabetic retinopathy reveals mediators of neurodegenerative brain diseases. / Sundstrom, Jeffrey; Hernández, Cristina; Weber, Sarah R.; Zhao, Yuanjun; Dunklebarger, Mitchell; Tiberti, Natalia; Laremore, Tatiana Nikolaevna; Simó-Servat, Olga; Garcia-Ramirez, Marta; Barber, Alistair; Gardner, Thomas W.; Simó, Rafael.

In: Investigative Ophthalmology and Visual Science, Vol. 59, No. 6, 01.05.2018, p. 2264-2274.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Proteomic analysis of early diabetic retinopathy reveals mediators of neurodegenerative brain diseases

AU - Sundstrom, Jeffrey

AU - Hernández, Cristina

AU - Weber, Sarah R.

AU - Zhao, Yuanjun

AU - Dunklebarger, Mitchell

AU - Tiberti, Natalia

AU - Laremore, Tatiana Nikolaevna

AU - Simó-Servat, Olga

AU - Garcia-Ramirez, Marta

AU - Barber, Alistair

AU - Gardner, Thomas W.

AU - Simó, Rafael

PY - 2018/5/1

Y1 - 2018/5/1

N2 - PURPOSE. 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. METHODS. 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. RESULTS. 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 with glial activation. The ‘‘Neuregulin Signaling,” “Synaptic Long Term Potentiation,” and “Amyloid Processing” pathways were enriched in diabetic retinas with no glial activation. CONCLUSIONS. Diabetes-induced retinal neurodegeneration and brain neurodegenerative diseases, 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 be useful to further understand the neurodegenerative processes that occur in the brain of persons with diabetes.

AB - PURPOSE. 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. METHODS. 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. RESULTS. 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 with glial activation. The ‘‘Neuregulin Signaling,” “Synaptic Long Term Potentiation,” and “Amyloid Processing” pathways were enriched in diabetic retinas with no glial activation. CONCLUSIONS. Diabetes-induced retinal neurodegeneration and brain neurodegenerative diseases, 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 be useful to further understand the neurodegenerative processes that occur in the brain of persons with diabetes.

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