TY - JOUR
T1 - Advanced glycation endproduct-induced aging of the retinal pigment epithelium and choroid
T2 - A comprehensive transcriptional response
AU - Tian, Jane
AU - Ishibashi, Kazuki
AU - Ishibashi, Kazuko
AU - Reiser, Karen
AU - Grebe, Rhonda
AU - Biswal, Shyam
AU - Gehlbach, Peter
AU - Handa, James T.
PY - 2005/8/16
Y1 - 2005/8/16
N2 - 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.
AB - 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.
KW - Basal deposit
KW - Bruch's membrane
KW - Transcriptome
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U2 - 10.1073/pnas.0504759102
DO - 10.1073/pnas.0504759102
M3 - Article
C2 - 16081535
AN - SCOPUS:23844507475
SN - 0027-8424
VL - 102
SP - 11846
EP - 11851
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 33
ER -