Role of an extracellular chaperone, Clusterin in the pathogenesis of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Biswajit Padhy; Gargi G. Nanda; Mahasweta Chowdhury; Debanand Padhi; Aparna Rao; Debasmita P. Alone

doi:10.1016/j.exer.2014.07.005

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Role of an extracellular chaperone, Clusterin in the pathogenesis of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Journal article

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Role of an extracellular chaperone, Clusterin in the pathogenesis of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Biswajit Padhy, Gargi G. Nanda, Mahasweta Chowdhury, Debanand Padhi, Aparna Rao and Debasmita P. Alone

Experimental eye research, Vol.127, pp.69-76

10/01/2014

DOI: 10.1016/j.exer.2014.07.005

PMID: 25057782

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Abstract

Pseudoexfoliation (PEX), an age related disorder is a prominent contributor to secondary glaucoma. Earlier studies have suggested involvement of clusterin in the development of PEX. We designed a case-control study to understand the role of clusterin single nucleotide polymorphisms (SNPs) in PEX and analyzed the role of risk alleles in the disease. Genotyping of SNPs in 136 PEX patients and 89 controls of Indian origin revealed a genetic association between rs2279590 and PEX in Indian population with a p-value of 0.004. The high risk allele “G” at rs2279590 has an effect on clusterin mRNA expression. There was a twofold higher clusterin mRNA level in “GG” genotyped individuals in comparison to “AA” genotyped individuals (p = 0.039). Western blot and immunohistochemistry studies showed an upregulation of Clusterin protein in pseudoexfoliation glaucoma (PXG) affected individuals in both aqueous humor and lens capsules respectively. Together, our results reveal that rs2279590 was found to be associated with PEX in Indian population and the risk allele mediates an allele specific upregulation of the clusterin mRNA. Moreover, upregulation of Clusterin protein in PXG individuals augments further protein deposition. •clusterin SNPs were studied in PEX and control subjects with Indian ethnicity.•rs2279590 was found to be associated with PEX with a p-value of 0.004.•Individuals with high risk allele “G” show higher clusterin mRNA expression.•Upregulation of Clusterin in PXG individuals augments further protein deposition.

clusterin

glaucoma

Indian population

pseudoexfoliation

Details

Title: Subtitle: Role of an extracellular chaperone, Clusterin in the pathogenesis of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma
Creators: Biswajit Padhy - National Institute of Science Education and Research
Gargi G. Nanda - National Institute of Science Education and Research
Mahasweta Chowdhury - L V Prasad Eye Institute
Debanand Padhi - L V Prasad Eye Institute
Aparna Rao - Glaucoma Services, LV Prasad Eye Institute, Bhubaneswar, Odisha, India
Debasmita P. Alone - School of Biological Sciences, NISER, Bhubaneswar, Odisha, India
Resource Type: Journal article
Publication Details: Experimental eye research, Vol.127, pp.69-76
DOI: 10.1016/j.exer.2014.07.005
PMID: 25057782
NLM abbreviation: Exp Eye Res
ISSN: 0014-4835
eISSN: 1096-0007
Publisher: Elsevier Ltd
Number of pages: 8
Language: English
Date published: 10/01/2014
Academic Unit: Internal Medicine
Record Identifier: 9985157628202771

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