RGD Reference Report - Increased clusterin expression in Fuchs' endothelial dystrophy. - Rat Genome Database

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Increased clusterin expression in Fuchs' endothelial dystrophy.

Authors: Jurkunas, UV  Bitar, MS  Rawe, I  Harris, DL  Colby, K  Joyce, NC 
Citation: Jurkunas UV, etal., Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2946-55. doi: 10.1167/iovs.07-1405. Epub 2008 Mar 31.
RGD ID: 8696020
Pubmed: PMID:18378577   (View Abstract at PubMed)
PMCID: PMC2789477   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.07-1405   (Journal Full-text)

PURPOSE: To investigate the differential expression of the glycoprotein clusterin/apoJ (CLU) in normal and Fuchs' endothelial dystrophy (FED) corneal endothelium and to compare the expression of various forms of CLU in normal and FED tissue. METHODS: FED and pseudophakic bullous keratopathy (PBK) corneal buttons were removed during transplantation, and normal corneas were obtained from tissue banks. Human corneal endothelial cells and Descemet's membrane (HCEC-DM) complex was dissected from the stroma. Proteins were separated on 2-D gels and subjected to comparative proteomic analysis. Relative expression of presecretory CLU (pre-sCLU), secretory (s)CLU, and nuclear (n)CLU were compared between normal and FED HCEC-DM by Western blot analysis. Expression of CLU mRNA was compared by using RT-PCR. Subcellular localization of CLU was compared in corneal wholemounts from normal eyes and eyes with FED by immunocytochemistry followed by confocal microscopy. RESULTS: Proteomic analysis revealed an apparent increase in CLU expression in FED HCEC-DM compared with the normal control. Western blot analysis demonstrated that pre-sCLU protein expression was 5.2 times higher in FED than in normal samples (P = 3.52E-05), whereas the mature form modified for secretion (sCLU) was not significantly elevated (P = 0.092). Expression of nCLU protein was significantly elevated in FED (P = 0.013). RT-PCR analysis revealed that CLU mRNA was significantly increased (P = 0.002) in FED samples, but not in PBK samples. CLU also had a distinctive localization in FED samples with enhanced intracellular staining around the guttae and in the nuclei of endothelial cells. CONCLUSIONS: CLU expression is markedly elevated in FED-affected tissue, pointing to a yet undiscovered form of dysregulation of endothelial cell function involved in FED pathogenesis.

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Clu  (clusterin)

Genes (Mus musculus)
Clu  (clusterin)

Genes (Homo sapiens)
CLU  (clusterin)

Additional Information