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

作者：Tian J; Ishibashi K; Ishibashi K; Reiser K; Grebe R; Biswal S; Gehlbach P; Handa JT^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2005, 102(33): 11846-11851.

DOI：10.1073/pnas.0504759102

• transcriptome
• basal deposit
• Bruch's membrane

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.

• 出版日期2005-8-16