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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:  Publisher    
Abstract/OtherAbstract:
Purpose: The purpose of our study was to investigate light damage induced transcript changes within neurosensory retina (NSR) and isolated RPE. Similar studies have been conducted previously, but were usually limited to the NSR and only a portion of the transcriptome. Herein we were able to query most of the transcriptome in not just NSR but also isolated RPE.Methods: Mice were exposed to 10,000 lux cool white fluorescent light for 18 hours and sacrificed 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, 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 the oxidative stress and complement system categories.Conclusions: We introduce the concept of a photo-oxidative stress induced vicious cycle of increased iron uptake leading to further oxidative stress.
Authors:
Majda Hadziahmetovic; Usha Kumar; Ying Song; Steven Grieco; Delu Song; Yafeng Li; John W Tobias; Joshua L Dunaief
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-26
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  -     ISSN:  1552-5783     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Perelman School of Medicine, University of Pennsylvania, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, PA, 19104, United States.
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