June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Molecular mechanisms in ocular surface disease of chronic Stevens-Johnson syndrome patients using tear proteomics
Author Affiliations & Notes
  • Madhuri Amulya Koduri
    Prof. Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, Telangana, India
    Manipal Academy of Higher Education, Manipal, Karnataka, India
  • Deeksha Prasad
    Prof. Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, Telangana, India
    Manipal Academy of Higher Education, Manipal, Karnataka, India
  • Abhinav Reddy Kethiri
    Prof. Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, Telangana, India
  • Swapna S Shanbhag
    Prof. Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, Telangana, India
    The Cornea Institute, LV Prasad Eye Institute, Hyderabad, Telangana, India
  • Sayan Basu
    Prof. Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, Telangana, India
    The Cornea Institute, LV Prasad Eye Institute, Hyderabad, Telangana, India
  • Vivek Singh
    Prof. Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, Telangana, India
  • Footnotes
    Commercial Relationships   Madhuri Amulya Koduri None; Deeksha Prasad None; Abhinav Reddy Kethiri None; Swapna S Shanbhag None; Sayan Basu None; Vivek Singh None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 957 – A0426. doi:
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      Madhuri Amulya Koduri, Deeksha Prasad, Abhinav Reddy Kethiri, Swapna S Shanbhag, Sayan Basu, Vivek Singh; Molecular mechanisms in ocular surface disease of chronic Stevens-Johnson syndrome patients using tear proteomics. Invest. Ophthalmol. Vis. Sci. 2022;63(7):957 – A0426.

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

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Abstract

Purpose : The chronic sequelae of Stevens-Johnson syndrome (SJS) can progress to various ocular complications and lead to visual impairment. The exact mechanism of the interplay of protein molecules in chronic ocular surface inflammation is not clearly understood. Therefore, this study aims to explore the underlying molecular signaling pathways to understand the disease process and mechanism of ocular damage using a proteomic approach.

Methods : Tear samples were collected from chronic SJS (n=6) with age-gender matched controls (n=6) and analyzed by liquid chromatography-mass spectroscopy for protein profiling and label-free quantification of tear proteins. Highly differentially regulated proteins were selected by z-score normalization followed by t-test significance using abundance values. The candidate proteins were shortlisted based on their presence in at least five patients with exclusive extracellular expression. Also, performed Ingenuity pathway analysis (IPA) to understand the differentially regulated canonical pathways in chronic SJS patients.

Results : The total tear proteins identified were ~1760, of which the t-test revealed 249 were differentially regulated proteins in chronic SJS tears. The results underline that 63 proteins were identified based on the extracellular expression, of which 33 proteins were significantly upregulated, including Neutrophil elastase (p<0.0001), Protein S100-A7 (p<0.0004), Neutrophil collagenase (p<0.0016), Myeloblastin (p<0.004), Myeloperoxidase (p<0.003), Matrilysin (p<0.04). And other 30 proteins were significantly downregulated, mostly related to lacrimal gland secretions. The IPA analysis of the significantly differentially regulated proteins revealed the IL-8 signaling pathway (p-value 1.24E-06) and inflammatory response (p-value 2.64E-04) as a major player in chronic SJS tears and could be correlated with disease conditions. Additionally, 33 proteins were uniquely expressing including Interleukin-36γ in SJS tear.

Conclusions : The findings of this study will contribute to a better understanding of the molecular mechanisms of chronic SJS ocular surface disease and may unravel new biological insights that help identify a potential therapeutic target for an effective treatment strategy.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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