Document Detail


Microarray analysis of murine retinal light damage reveals changes in iron regulatory, complement, and antioxidant genes in the neurosensory retina and isolated RPE.
MedLine Citation:
PMID:  22736611     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The purpose of this study was to investigate light damage-induced transcript changes within neurosensory retina (NSR) and isolated retinal pigment epithelium (RPE). Similar studies have been conducted previously, but were usually limited to the NSR and only a portion of the transcriptome. Herein most of the transcriptome, not just in the NSR but also in isolated RPE, was queried.
METHODS: Mice were exposed to 10,000 lux cool white fluorescent light for 18 hours and euthanized 4 hours after photic injury. NSR and isolated RPE were collected, and RNA was isolated. DNA microarray hybridization was conducted as described in the Affymetrix GeneChip Expression Analysis Technical Manual. Microarray analysis was performed using probe intensity data derived from the Mouse Gene 1.0 ST Array. For the genes of interest, confirmation of gene expression was done using quantitative real-time PCR. Immunofluorescence assessed protein levels and localization.
RESULTS: Numerous iron regulatory genes were significantly changed in the light-exposed NSR and RPE. Several of these gene expression changes favored an iron-overloaded state. For example, the transferrin receptor was upregulated in both light-exposed NSR and RPE. Consistent with this, there was stronger transferrin receptor immunoreactivity in the light-exposed retinas. Significant changes in gene expression following light damage were also observed in oxidative stress and complement system genes.
CONCLUSIONS: The concept of a photooxidative stress-induced vicious cycle of increased iron uptake leading to further oxidative stress was introduced.
Authors:
Majda Hadziahmetovic; Usha Kumar; Ying Song; Steven Grieco; Delu Song; Yafeng Li; John W Tobias; Joshua L Dunaief
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-07
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  53     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-08     Completed Date:  2012-10-24     Revised Date:  2014-10-16    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5231-41     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / physiology*
Complement System Proteins / genetics*
Fluorescent Antibody Technique
Gene Expression
Homeostasis / radiation effects
Iron / metabolism
Iron-Regulatory Proteins / genetics*
Light / adverse effects*
Male
Mice
Mice, Inbred BALB C
Microarray Analysis
Oxidative Stress / physiology
Real-Time Polymerase Chain Reaction
Retina / metabolism*,  radiation effects
Retinal Pigment Epithelium / metabolism
Grant Support
ID/Acronym/Agency:
EY015240/EY/NEI NIH HHS; R01 EY015240/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Iron-Regulatory Proteins; 9007-36-7/Complement System Proteins; E1UOL152H7/Iron
Comments/Corrections

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