June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Augmentation of CFTR function combined with rescue of vitamin D receptor degradation mitigates hyperosmotic stress-induced inflammation in dry eye disease.
Author Affiliations & Notes
  • Anuprita Ghosh
    GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India
  • Trailokyanath Panigrahi
    GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India
  • Sharon D'Souza
    Narayana Nethralaya, Bangalore, India
  • Rohit Shetty
    Narayana Nethralaya, Bangalore, India
  • Arkasubhra Ghosh
    GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India
  • Swaminathan Sethu
    GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India
  • Footnotes
    Commercial Relationships   Anuprita Ghosh, None; Trailokyanath Panigrahi, None; Sharon D'Souza, None; Rohit Shetty, None; Arkasubhra Ghosh, None; Swaminathan Sethu, None
  • Footnotes
    Support  SERB-DST (ECR-2216-000443); Govt. of India; VGST-CESEM-GRD455, Govt. of India.
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 141. doi:
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      Anuprita Ghosh, Trailokyanath Panigrahi, Sharon D'Souza, Rohit Shetty, Arkasubhra Ghosh, Swaminathan Sethu; Augmentation of CFTR function combined with rescue of vitamin D receptor degradation mitigates hyperosmotic stress-induced inflammation in dry eye disease.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):141.

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

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Abstract

Purpose : Dry eye disease (DED) signs and symptoms are causally associated with increased ocular surface (OS) inflammation. Modulation of key regulators of aberrant OS inflammation is ongoing. We investigated the relevance of harnessing the function of cystic fibrosis transmembrane conductance regulator (CFTR) and vitamin D receptor (VDR) in managing DED.

Methods : Conjunctival impression cytology (CIC) samples were collected from control subjects (n=15) and DED patients (n=15) following written, informed consent and institutional ethics committee approval. Cells from CIC were used to determine the status of CFTR, VDR, hyperosmotic stress indicator (TonEBP), inflammatory factors (IL-6, IL-8, IL-17A, TNFα, MMP9) and intracellular chloride ion indicator (GLRX5) by qPCR and/or immunofluorescence. SV40-immortalized human corneal epithelial cells (HCECs) were used to study the effect of CFTR activator (CA) and vitamin D (VD) in hyperosmotic stress (HOs)-induced response in an in vitro DED model. qPCR and/or western blotting were used to determine the expression status of the genes mentioned earlier, along with p-p38.

Results : Significantly, higher expression of inflammatory factors, TonEBP, GLRX5 and reduced VDR were observed in DED patients. Positive correlation (P<0.05) was observed between expression of TonEBP and inflammatory genes in DED patients. Similar observations were made in HOs-induced HCECs in vitro. In addition, to the reduction of HOs-induced GLRX5, inflammatory gene expression and p-p38, CA was also observed to abate HOs-induced VDR degradation. Further, combination of CA and VD reduced HOs-induced TonEBP expression, in addition to the reduction of other factors stated earlier.

Conclusions : CFTR activator and vitamin D mitigates hyperosmotic stress induced response in HCECs. CA and VD – both commonly available and with history of use in humans can be used in combination topically for the management of DED.

This is a 2020 ARVO Annual Meeting abstract.

 

Altered status of TonEBP, VDR and GLRX5 in patients with DED

Altered status of TonEBP, VDR and GLRX5 in patients with DED

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