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Aquaporin expression in blood-retinal barrier cells during experimental autoimmune uveitis.
- Source :
-
Molecular vision [Mol Vis] 2010 Apr 03; Vol. 16, pp. 602-10. Date of Electronic Publication: 2010 Apr 03. - Publication Year :
- 2010
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Abstract
- Purpose: Blood-retinal barrier (BRB) breakdown and retinal edema are major complications of autoimmune uveitis and could be related to deregulation of aquaporin (AQP) expression. We have therefore evaluated the expression of AQP1 and AQP4 on BRB cells during experimental autoimmune uveitis (EAU) in mice.<br />Methods: C57Bl6 mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 1-16. The disease was graded clinically, and double immunolabeling using glial fibrillary acidic protein (GFAP; a marker of disease activity) and AQP1 or AQP4 antibodies was performed at day 28. AQP1 expression was also investigated in mouse retinal pigment epithelium (RPE) cells (B6-RPE07 cell line) by reverse transcriptase PCR and western blot under basal and tumor necrosis factor alpha (TNF-alpha)-stimulated conditions.<br />Results: In both normal and EAU retina, AQP1 and AQP4 expression were restricted to the photoreceptor layer and to the Müller cells, respectively. Retinal endothelial cells never expressed AQP1. In vasculitis and intraretinal inflammatory infiltrates, decreased AQP1 expression was observed due to the loss of photoreceptors and the characteristic radial labeling of AQP4 was lost. On the other hand, no AQP4 expression was detected in RPE cells. AQP1 was strongly expressed by choroidal endothelial cells, rendering difficult the evaluation of AQP1 expression by RPE cells in vivo. No major differences were found between EAU and controls at this level. Interestingly, B6-RPE07 cells expressed AQP1 in vitro, and TNF-alpha downregulated AQP1 protein expression in those cells.<br />Conclusions: Changes in retinal expression of AQP1 and AQP4 during EAU were primarily due to inflammatory lesions, contrasting with major modulation of AQP expression in BRB detected in other models of BRB breakdown. However, our data showed that TNF-alpha treatment strongly modulates AQP1 expression in B6-RPE07 cells in vitro.
- Subjects :
- Animals
Aquaporin 1 genetics
Cell Line
Epithelial Cells metabolism
Epithelial Cells pathology
Gene Expression Regulation
Glial Fibrillary Acidic Protein metabolism
Mice
Mice, Inbred C57BL
Pigment Epithelium of Eye metabolism
Pigment Epithelium of Eye pathology
RNA, Messenger genetics
RNA, Messenger metabolism
Uveitis chemically induced
Aquaporin 1 metabolism
Aquaporin 4 metabolism
Blood-Retinal Barrier metabolism
Blood-Retinal Barrier pathology
Uveitis metabolism
Uveitis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-0535
- Volume :
- 16
- Database :
- MEDLINE
- Journal :
- Molecular vision
- Publication Type :
- Academic Journal
- Accession number :
- 20383338