Population Differences in Elastin Maturation in Optic Nerve Head Tissue and Astrocytes
Autor: | Vishwanathan Hucthagowder, Barry C. Starcher, Olga A. Agapova, M. Rosario Hernandez, Zsolt Urban, Ping Yang |
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Rok vydání: | 2007 |
Předmět: |
Male
medicine.medical_specialty Pathology genetic structures Blotting Western Optic Disk Population Cell Culture Techniques Radioimmunoassay Optic disk Black People Lysyl oxidase macromolecular substances White People Protein-Lysine 6-Oxidase chemistry.chemical_compound Internal medicine Glial Fibrillary Acidic Protein medicine Humans RNA Messenger Fluorescent Antibody Technique Indirect education education.field_of_study integumentary system LOXL2 biology Tropoelastin Reverse Transcriptase Polymerase Chain Reaction Chemistry Middle Aged Tissue Donors eye diseases Elastin Desmosine Endocrinology Astrocytes Optic nerve biology.protein Electrophoresis Polyacrylamide Gel Female sense organs |
Zdroj: | Investigative Opthalmology & Visual Science. 48:3209 |
ISSN: | 1552-5783 |
DOI: | 10.1167/iovs.07-0107 |
Popis: | PURPOSE. Glaucomatous optic neuropathy is characterized by remodeling of the extracellular matrix with disorganization of elastic fibers in the optic nerve head (ONH). There are significant differences in prevalence of glaucomatous optic neuropathy between African Americans (AAs) and Caucasian Americans (CAs). The goal of this study was to evaluate differences in elastin synthesis and maturation in ONH tissue and cells of AA and CA donors with no eye disease, to provide a basis for underlying racial differences in susceptibility to elevated intraocular pressure. METHODS. The amount of mature elastin in ONHs from each group of donors was evaluated by desmosine radioimmunoassay. The distribution of elastic fibers in ONH tissue was investigated by immunofluorescent staining. Elastin and lysyl oxidase mRNA levels and alternative splicing of elastin in ONH astrocytes were investigated by quantitative PCR. Tropoelastin protein expression was assessed by immunoblot analysis. RESULTS. ONHs from AA donors had significantly reduced levels of desmosine compared with those of CAs. In contrast, elastin mRNA and tropoelastin synthesis were elevated in ONH astrocytes from AA individuals. The inclusion of exon 23 in elastin mRNA and lysyl oxidase-like 2 mRNA levels was significantly reduced in astrocytes from AA compared with CA donors. CONCLUSIONS. A reduced number of cross-linking domains in elastin and decreased lysyl oxidase-like 2 expression leads to decreased amount of mature elastin in ONHs from healthy AA individuals compared with CA donors. These results suggest ELN and LOXL2 as candidate susceptibility genes for population-specific genetic risk of primary open-angle glaucoma (POAG). (Invest Ophthalmol Vis Sci. 2007;48:3209‐3215) |
Databáze: | OpenAIRE |
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