June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Expression analysis of primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 in ocular tissues of glaucoma patients and controls
Author Affiliations & Notes
  • Eranga Nishanthie Vithana
    Singapore Eye Research Institute, Singapore, Singapore
    Duke-NUS Graduate Medical School, Singapore, Singapore
  • Mei Chin Lee
    Singapore Eye Research Institute, Singapore, Singapore
    Duke-NUS Graduate Medical School, Singapore, Singapore
  • William Shei
    Singapore Eye Research Institute, Singapore, Singapore
  • Monisha Nongpiur
    Singapore Eye Research Institute, Singapore, Singapore
    Duke-NUS Graduate Medical School, Singapore, Singapore
  • Chiea Chuen Khor
    Genome institute of Singapore, Singapore, Singapore
    Department of Biochemistry, National University of Singapore, Singapore, Singapore
  • Tin Aung
    Singapore Eye Research Institute, Singapore, Singapore
    Glaucoma, Singapore National Eye Center, Singapore, Singapore
  • Walter Hunziker
    Institute of Molecular and Cell Biology, Singapore, Singapore
    Department of Physiology, National University of Singapore, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Eranga Vithana, None; Mei Chin Lee, None; William Shei, None; Monisha Nongpiur, None; Chiea Chuen Khor, None; Tin Aung, None; Walter Hunziker, None
  • Footnotes
    Support  This work is supported by the National Medical Research Council (NMRC) in Singapore, Ref: NMRC/CBRG/0032/2013
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2137. doi:
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    • Get Citation

      Eranga Nishanthie Vithana, Mei Chin Lee, William Shei, Monisha Nongpiur, Chiea Chuen Khor, Tin Aung, Walter Hunziker; Expression analysis of primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 in ocular tissues of glaucoma patients and controls. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2137.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The C allele of the intragenic SNP rs11024102 within PLEKHA7, is associated with increased risk of PACG. To investigate its role in PACG pathogenesis, we compared PLEKHA7 expression levels between control (non-glaucoma), PACG and primary open angle glaucoma (POAG) subjects.

Methods : Lens capsules were obtained from 29 controls, 36 PACG and 35 POAG Chinese subjects undergoing lens phacoemulsification. Iris tissue was collected from 20 PACG and 20 POAG subjects during trabeculectomy. PLEKHA7 mRNA expression was analysed by real-time qPCR using GAPDH for normalization. Fold changes in PLEKHA7 gene expression in lens capsules of PACG and POAG was compared against non-glaucoma subjects, whereas PLEKHA7 expression in iris was compared between PACG and POAG subjects. Two-tailed Student’s t test was used to determine differences between groups, with significance determined at p<0.05.

Results : PLEKHA7 gene expression in PACG lens capsules was significantly reduced compared to the non-glaucoma control lens capsules (0.72±0.05, p=8.89×10-7). This was not observed for POAG samples (0.91±0.14, p=0.253). PLEKHA7 gene expression in PACG iris tissues was also significantly reduced compared to POAG (0.82±0.15, p=0.0015). Next we stratified our PACG lens capsule samples (N=27) by their genotypes (risk C/C, non-risk T/T, and heterozygous C/T) with respect to rs11024102 and analyzed the expression level of PLEKHA7. Genotyping indicated 40.8% of the PACG cases to be (T/T), 33.3% to be C/T and 25.9% to be homozygous for the risk allele (C/C). In PACG lens capsules, PLEKHA7 mRNA expression was significantly down regulated by 26.3±0.11% (p=0.004) in heterozygotes and by 14.95±0.09% (p=0.026) in the homozygous risk allele carriers when compared with homozygous non-risk allele carriers. In POAG patients the expression of PLEKHA7 was not significantly different between the three genotypes.

Conclusions : PLEKHA7 expression is down regulated in lens epithelial cells and iris tissues of PACG patients. PLEKHA7 expression in PACG lens capsules is correlated with the presence of the risk allele of SNP rs11024102. PLEKHA7 co-localizes with apical junctional complexes of cells of the blood aqueous barrier, we therefore postulate that low PLEKHA7 expression levels may lead to a possible dysregulation of the BAB and contribute to PACG pathogenesis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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