Advanced glycation endproduct-induced aging of the retinal pigment epithelium and choroid: A comprehensive transcriptional response

Jane Tian, Kazuki Ishibashi, Kazuko Ishibashi, Karen Reiser, Rhonda Grebe, Shyam Biswal, Peter Gehlbach, James T. Handa

Research output: Contribution to journalArticle

Abstract

Advanced glycation endproduct (AGE) formation is a trigger for the onset of age-related disease. To evaluate AGE-induced change in the ocular fundus, 5-mo-old C57BL/6 mice were given low-dose D-galactose (D-gal) for 8 wk and evaluated by AGE fluorescence, electroretinography (ERG), electron microscopy, and microarray analysis for 20 wk. Although AGE fluorescence was increased in D-gal-treated retinal pigment epithelium (RPE)-choroid compared with controls at all time points, ERG showed no AGE-induced functional toxicity. Progressive ultrastructural aging in the RPE-choroid was associated temporally with a transcriptional response of early inflammation, matrix expansion, and aberrant lipid processing and, later, down-regulation of energy metabolism genes, up-regulation of crystallin genes, and altered expression of cell structure genes. The overall transcriptome is similar to the generalized aging response of unrelated cell types. A subset of transcriptional changes is similar to early atherosclerosis, a chronic inflammatory disease characterized by matrix expansion and lipid deposition. These changes suggest an important contribution of a single environmental stimulus to the complex aging response.

Original languageEnglish (US)
Pages (from-to)11846-11851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number33
DOIs
StatePublished - Aug 16 2005

Keywords

  • Basal deposit
  • Bruch's membrane
  • Transcriptome

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Advanced glycation endproduct-induced aging of the retinal pigment epithelium and choroid: A comprehensive transcriptional response'. Together they form a unique fingerprint.

  • Cite this