Human retinal pigment epithelium proteome changes in early diabetes

A. Decanini, P. R. Karunadharma, C. L. Nordgaard, X. Feng, T. W. Olsen, D. A. Ferrington

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Aims/hypothesis: Diabetic retinopathy is the most common complication of diabetes and a leading cause of blindness among working-age adults. Anatomical and functional changes occur in the retina and retinal pigment epithelium (RPE) prior to clinical symptoms of the disease. However, the molecular mechanisms responsible for these early changes, particularly in the RPE, remain unclear. To begin defining the molecular changes associated with pre-retinopathic diabetes, we conducted a comparative proteomics study of human donor RPE. Methods: The RPE was dissected from diabetic human donor eyes with no clinically apparent diabetic retinopathy (n=6) and from eyes of age-matched control donors (n=17). Soluble proteins were separated based upon their mass and charge using two-dimensional (2-D) gel electrophoresis. Protein spots were visualised with a fluorescent dye and spot densities were compared between diabetic and control gels. Proteins from spots with significant disease-related changes in density were identified using mass spectrometry. Results: Analysis of 325 spots on 2-D gels identified 31 spots that were either up- or downregulated relative to those from age-matched control donors. The protein identity of 18 spots was determined by mass spectrometry. A majority of altered proteins belonged to two major functional groups, metabolism and chaperones, while other affected categories included protein degradation, synthesis and transport, oxidoreductases, cytoskeletal structure and retinoid metabolism. Conclusions/interpretation: Changes identified in the RPE proteome of pre-retinopathic diabetic donor eyes compared with age-matched controls suggest specific cellular alterations that may contribute to diabetic retinopathy. Defining the pre-retinopathic changes affecting the RPE could provide important insight into the molecular events that lead to this disease.

Original languageEnglish (US)
Pages (from-to)1051-1061
Number of pages11
JournalDiabetologia
Volume51
Issue number6
DOIs
StatePublished - Jun 1 2008

Fingerprint

Retinal Pigment Epithelium
Proteome
Diabetic Retinopathy
Proteins
Mass Spectrometry
Gels
Retinoids
Electrophoresis, Gel, Two-Dimensional
Protein Transport
Diabetes Complications
Blindness
Fluorescent Dyes
Proteomics
Proteolysis
Retina
Oxidoreductases
Down-Regulation

Keywords

  • 2-D gels
  • Diabetes
  • Human donor eyes
  • MALDI-TOF mass spectrometry
  • Pre-retinopathic
  • Proteomics
  • Retina
  • Retinal pigment epithelium

Cite this

Decanini, A., Karunadharma, P. R., Nordgaard, C. L., Feng, X., Olsen, T. W., & Ferrington, D. A. (2008). Human retinal pigment epithelium proteome changes in early diabetes. Diabetologia, 51(6), 1051-1061. https://doi.org/10.1007/s00125-008-0991-2

Human retinal pigment epithelium proteome changes in early diabetes. / Decanini, A.; Karunadharma, P. R.; Nordgaard, C. L.; Feng, X.; Olsen, T. W.; Ferrington, D. A.

In: Diabetologia, Vol. 51, No. 6, 01.06.2008, p. 1051-1061.

Research output: Contribution to journalArticle

Decanini, A, Karunadharma, PR, Nordgaard, CL, Feng, X, Olsen, TW & Ferrington, DA 2008, 'Human retinal pigment epithelium proteome changes in early diabetes', Diabetologia, vol. 51, no. 6, pp. 1051-1061. https://doi.org/10.1007/s00125-008-0991-2
Decanini A, Karunadharma PR, Nordgaard CL, Feng X, Olsen TW, Ferrington DA. Human retinal pigment epithelium proteome changes in early diabetes. Diabetologia. 2008 Jun 1;51(6):1051-1061. https://doi.org/10.1007/s00125-008-0991-2
Decanini, A. ; Karunadharma, P. R. ; Nordgaard, C. L. ; Feng, X. ; Olsen, T. W. ; Ferrington, D. A. / Human retinal pigment epithelium proteome changes in early diabetes. In: Diabetologia. 2008 ; Vol. 51, No. 6. pp. 1051-1061.
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N2 - Aims/hypothesis: Diabetic retinopathy is the most common complication of diabetes and a leading cause of blindness among working-age adults. Anatomical and functional changes occur in the retina and retinal pigment epithelium (RPE) prior to clinical symptoms of the disease. However, the molecular mechanisms responsible for these early changes, particularly in the RPE, remain unclear. To begin defining the molecular changes associated with pre-retinopathic diabetes, we conducted a comparative proteomics study of human donor RPE. Methods: The RPE was dissected from diabetic human donor eyes with no clinically apparent diabetic retinopathy (n=6) and from eyes of age-matched control donors (n=17). Soluble proteins were separated based upon their mass and charge using two-dimensional (2-D) gel electrophoresis. Protein spots were visualised with a fluorescent dye and spot densities were compared between diabetic and control gels. Proteins from spots with significant disease-related changes in density were identified using mass spectrometry. Results: Analysis of 325 spots on 2-D gels identified 31 spots that were either up- or downregulated relative to those from age-matched control donors. The protein identity of 18 spots was determined by mass spectrometry. A majority of altered proteins belonged to two major functional groups, metabolism and chaperones, while other affected categories included protein degradation, synthesis and transport, oxidoreductases, cytoskeletal structure and retinoid metabolism. Conclusions/interpretation: Changes identified in the RPE proteome of pre-retinopathic diabetic donor eyes compared with age-matched controls suggest specific cellular alterations that may contribute to diabetic retinopathy. Defining the pre-retinopathic changes affecting the RPE could provide important insight into the molecular events that lead to this disease.

AB - Aims/hypothesis: Diabetic retinopathy is the most common complication of diabetes and a leading cause of blindness among working-age adults. Anatomical and functional changes occur in the retina and retinal pigment epithelium (RPE) prior to clinical symptoms of the disease. However, the molecular mechanisms responsible for these early changes, particularly in the RPE, remain unclear. To begin defining the molecular changes associated with pre-retinopathic diabetes, we conducted a comparative proteomics study of human donor RPE. Methods: The RPE was dissected from diabetic human donor eyes with no clinically apparent diabetic retinopathy (n=6) and from eyes of age-matched control donors (n=17). Soluble proteins were separated based upon their mass and charge using two-dimensional (2-D) gel electrophoresis. Protein spots were visualised with a fluorescent dye and spot densities were compared between diabetic and control gels. Proteins from spots with significant disease-related changes in density were identified using mass spectrometry. Results: Analysis of 325 spots on 2-D gels identified 31 spots that were either up- or downregulated relative to those from age-matched control donors. The protein identity of 18 spots was determined by mass spectrometry. A majority of altered proteins belonged to two major functional groups, metabolism and chaperones, while other affected categories included protein degradation, synthesis and transport, oxidoreductases, cytoskeletal structure and retinoid metabolism. Conclusions/interpretation: Changes identified in the RPE proteome of pre-retinopathic diabetic donor eyes compared with age-matched controls suggest specific cellular alterations that may contribute to diabetic retinopathy. Defining the pre-retinopathic changes affecting the RPE could provide important insight into the molecular events that lead to this disease.

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