June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Epithelial-Mesenchymal Transition (EMT) predeposition in Aged related macular degeneration (AMD) pathology with immune infiltrate - a triad interplay
Author Affiliations & Notes
  • Chang Kao-Jung
    National Yang-Ming University, Taichung, Taiwan
  • Footnotes
    Commercial Relationships   Chang Kao-Jung, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2291. doi:
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      Chang Kao-Jung; Epithelial-Mesenchymal Transition (EMT) predeposition in Aged related macular degeneration (AMD) pathology with immune infiltrate - a triad interplay. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2291.

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

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Abstract

Purpose : The pathology upstream to aged related macular degeneration (AMD) is still largely unclear. Judging from the Hypoxia condition alongside reactive oxygen species (ROS) insult in AMD, we postulate an oxidative stress driven Epithelial-Mesenchymal transition (EMT) took place in the retinal pigmented epithelium (RPE) layer, and this conversion crucialy alters RPE with its obligatory function, such as phagocytosis and blood retinal barrier. A condition mimicing experiment was carried out to investigate how oxidative stress may have perturbate RPE operations, so as to lead to aged related macular degeneration (AMD).

Methods : In aim to mimic oxidative challenges in AMD conditions, 500µM H2O2 additioned medium and hypoxic chamber cultures were established. EMT phenomenon was confirmed by western, immunoflourescence, and qPCR results. Immune engagement following RPE EMT was investigated by invert transwell migration assay and ELISA quantification of supernatant cytokines. FITC-conjugated of porcine photoreceptor outer segment (POS) was fed to the RPE cultures in order to quantify RPE phagocytic ability under EMT perturbations.

Results : Under oxidative challenges, western blots of RPE cultures showed a full expression of canonical EMT trancription factors, including Snail/ Slug/ Twist. Immune infiltrate was confirmed by the migration assay, and was noted to enhance EMT predepositions in RPE cultures. Phagocytic capability was also tested in such EMT conditions, finding a general decreased POS engulfment in both H2O2 treated and hypoxia conditions (p=0.023 and p=0.0086 respectively).

Conclusions : In oxidative stressed AMD conditions, EMT occurence in RPE layers will disturb ordinary ocular well-beings. Such mesenchymal transition deprive epithelium of its obligated functions of upholding immune privilege and photoreceptor recycling. Thus, the following immune infiltrate, complement body activation, and lipid homeostasis breakdown can lead to a worsened drusen accumulates. This thickened drusen can feed into oxidative stresses, and mediates a secondary EMT in RPE, forming a vicious [hypoxia-EMT-drusen-hypoxia] cycle in AMD pathology.

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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