Linked Life Data

16109308

Source:http://linkedlifedata.com/resource/pubmed/id/16109308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-8-19
pubmed:abstractText
The pathogenesis of age-related macular degeneration (AMD) is still unknown but there is growing evidence that a combination of both oxidative injury and genetic factors may play a role. One particle hypothesis proposes that dysregulation of multiple genes in response to an oxidative injury could contribute to the development of AMD. While direct examination of ocular cells from AMD patients is difficult, AMD also appears to have a systemic component. Therefore, as is the case with other central nervous diseases, peripheral sites may also manifest any underlying genetic abnormalities. For the present study, biopsy-derived fibroblasts from 4 patients with the early form and 4 patients with the late form of AMD and 3 age-matched control patients were grown in culture and treated with a nonlethal dose of the oxidative stimulus menadione. Gene expression patterns were quantitatively and qualitatively examined using Human Genome U95A GeneChips (Affymetrix) and verified by real-time PCR analysis. In response to the oxidative injury 755 genes were found to be upregulated at least twofold in one of the patients groups. Cluster analysis of expression profiles detected six patterns of dysregulation initiated by oxidative injury specific for the disease groups (98 genes total). Clusters of genes dysregulated by the sublethal oxidative injury in either early and/or late AMD groups were further categorized by overrepresentation of GO "biological process" categories using Expression Analysis Systematic Explorer (EASE) software. This approach demonstrated that four major functional gene groups including inflammatory/innate immune response, transcriptional regulation, cell cycle, and proliferation were significantly overrepresented (Fisher test ranging from 0.0393 to 0.00018) in both AMD patients groups in response to the oxidative injury. Despite the small number of patients in the study, specific biological and statistical differences in gene expression profiles between control and AMD patients were identified but only in the presence of an environmental stimulus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
781-96
pubmed:meshHeading
pubmed-meshheading:16109308-Aged, pubmed-meshheading:16109308-Aged, 80 and over, pubmed-meshheading:16109308-Biopsy, pubmed-meshheading:16109308-Case-Control Studies, pubmed-meshheading:16109308-Cell Proliferation, pubmed-meshheading:16109308-Cluster Analysis, pubmed-meshheading:16109308-Collagen Type I, pubmed-meshheading:16109308-Fibroblasts, pubmed-meshheading:16109308-Gene Expression Regulation, pubmed-meshheading:16109308-Humans, pubmed-meshheading:16109308-Immunohistochemistry, pubmed-meshheading:16109308-Indicators and Reagents, pubmed-meshheading:16109308-Inflammation, pubmed-meshheading:16109308-Macular Degeneration, pubmed-meshheading:16109308-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16109308-Oxidative Stress, pubmed-meshheading:16109308-Oxygen, pubmed-meshheading:16109308-RNA, pubmed-meshheading:16109308-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16109308-Skin, pubmed-meshheading:16109308-Tetrazolium Salts, pubmed-meshheading:16109308-Vitamin K 3
pubmed:year
2005
pubmed:articleTitle
Differences in gene expression profiles in dermal fibroblasts from control and patients with age-related macular degeneration elicited by oxidative injury.
pubmed:affiliation
National Eye Institute, Bethesda, MD 20892-1857, USA.
pubmed:publicationType
Journal Article