Macula-less rat and macula-bearing monkey retinas exhibit common lifelong proteomic changes

Neurobiol Aging. 2013 Nov;34(11):2659-75. doi: 10.1016/j.neurobiolaging.2013.04.020. Epub 2013 May 30.

Abstract

The visual consequences of age-related alterations in the neural retina have been well documented, but little is known about their molecular bases. We performed a comparative proteomic analysis of the retinas in marmosets and rats to identify proteins for which the expression profiles are altered with maturation and aging. Protein profiles were compared in the newborn, juvenile, middle-age, and aged retinas using 2-dimensional gel electrophoresis. Matrix-assisted desorption ionization-time-of-flight mass spectrometry revealed common proteins in rats and marmosets that exhibited changes in concentration throughout life. Western blot, quantitative reverse-transcriptase polymerase chain reaction, and immunohistochemistry analyses of selected proteins and their mRNA were used to determine whether the changes identified by proteomics were verifiable at the cellular and molecular levels. We found 4 proteins common to both species (Parkinson disease [autosomal recessive, early onset] 7/DJ-1, stathmin, peroxiredoxin, and β-synuclein) whose concentrations were regulated with age. These findings were confirmed by Western blot, immunohistochemistry, and quantitative reverse-transcriptase polymerase chain reaction analyses. The proteins were localized in certain layers and subsets of cells within the retinas of both species. The expression of these proteins in the adult human retina was confirmed with immunohistochemistry. The present study is the first to provide evidence that the retina is physiologically characterized by specific lifelong changes in its proteome. These changes are independent of whether the retina bears a macula, occur in key functional pathways during the processing of visual signals, and might be involved in the development of age-related pathologic entities.

Keywords: Aging retina; Macula; Mammals; Protein expression; Proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / metabolism*
  • Animals
  • Animals, Newborn
  • Callithrix
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Developmental / physiology*
  • Humans
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Neurons / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Peroxiredoxins / genetics
  • Peroxiredoxins / metabolism
  • Protein Deglycase DJ-1
  • Proteome / genetics
  • Proteome / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / cytology
  • Retina / growth & development
  • Retina / metabolism*
  • Stathmin / genetics
  • Stathmin / metabolism
  • Young Adult
  • beta-Synuclein / genetics
  • beta-Synuclein / metabolism

Substances

  • Eye Proteins
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Proteome
  • Stathmin
  • beta-Synuclein
  • Peroxiredoxins
  • PARK7 protein, human
  • Protein Deglycase DJ-1