Abstract
Purpose:
The visual consequences of age-related alterations in the neural retina are well documented, but little is known about their molecular bases. We performed a comparative proteomic analysis of the retinae in marmosets and rats, in order to identify proteins for which the expression profiles in retinas are altered with age.
Methods:
Protein profiles were compared in the newborn, juvenile, middle-aged, and aged retinae using two-dimensional gel electrophoresis. Seven proteins exhibited changes in content throughout the life of rats, and 21 proteins that exhibited age-related content changes in marmosets were identified by matrix-assisted desorption ionization-time-of-flight mass spectrometry. Western-blot (WB), quantitative reverse-transcriptase PCR (qRT-PCR), and immunohistochemistry (IHC) analyses of selected proteins and their mRNA were employed to determine whether changes identified by proteomics were verifiable at the cellular and molecular levels.
Results:
We found four proteins common to both species [Parkinson disease (autosomal recessive, early onset) 7/DJ-1, stathmin, peroxiredoxin, and β-synuclein] whose contents were regulated with age. WB, IHC, and qRT-PCR analyses confirmed these findings. The proteins were localized in certain layers and subsets of cells within the retinae of both species. Alterations in the expressions of these proteins between the localization of the macular and retinal periphery were analyzed with IHC. Detection of found proteins in the adult human retina were confirmed with IHC.
Conclusions:
This study is the first to provide evidence that the aging retina is physiologically characterized by specific changes in its proteome. These changes occur in key functional pathways during the processing of visual signals and may be involved in the development of age-related pathologies, such as age-related macular degeneration.
Keywords: 413 aging •
688 retina •
663 proteomics