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Ocular surface sphingolipids associate with the refractory nature of vernal keratoconjunctivitis: newer insights in VKC pathogenesis
  1. Vignesh Menta1,
  2. Shweta Agarwal2,
  3. Ujjalkumar Subhash Das3,
  4. Laxmi Moksha3,
  5. Gurumurthy Srividya1,
  6. Amrutha M Anandan2,
  7. Bhaskar Srinivasan2,
  8. Geetha Iyer2,
  9. Thirumurthy Velpandian3,
  10. Narayanasamy Angayarkanni1
  1. 1R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, Tamil Nadu, India
  2. 2C.J. Shah Cornea Services, Dr G Sitalaksmi Memorial Clinic for Ocular Surface Disorders, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
  3. 3Ocular Pharmacology and Pharmacy Division, All India Institute of Medical Sciences, New Delhi, India
  1. Correspondence to Dr Narayanasamy Angayarkanni, R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai-600006, India; drak{at}snmail.org; Dr Shweta Agarwal; doctorshwetaa{at}gmail.com

Abstract

Background The etiopathogenesis of vernal keratoconjunctivitis (VKC) is incompletely understood. Bioactive lipids play a key role in allergic disorders. This study focused on the sphingolipid metabolism on the ocular surface of VKC and to explore if it has a contributory role in the refractoriness of the disease.

Methods Active VKC cases, (n=87) (classified as mild/moderate and severe/very severe based on the disease symptoms) and age-matched healthy controls (n=60) were recruited as part of a 2-year prospective study at a tertiary eye care centre in South India. Conjunctival imprint cytology was used to assess gene expression of enzymes of sphingolipids metabolism. Sphingolipids were estimated in the tears by LC-MS/MS analysis. In vitro study was done to assess IgE-induced alterations in sphingosine-1-phosphate (S1P) receptor expression and histone modification in cultured mast cells.

Results Significantly altered gene expression of the sphingolipids enzymes and S1P receptor (SIP3R) were observed in conjunctival imprint cells of VKC cases. Pooled tears analysis revealed significantly lowered levels of S1P(d17:0), S1P(d20:1) (p<0.001) and S1P(d17:1) (p<0.01) specifically in severe/very severe VKC compared with both mild/moderate VKC and control. Cer(d18:/17:0) (p<0.001), ceramide-1-phosphate (C1P)(d18:1/8:0) (p<0.01) and C1P(d18:1/2.0 (p<0.05) were lowered in severe/very severe VKC compared with mild/moderate VKC. Cultured mast cells treated with IgE revealed significantly increased gene expression of S1P1 and 3 receptors and the protein expression of histone deacetylases (1, 6).

Conclusion Altered sphingolipid metabolism in the ocular surface results in low tear ceramide and sphingosine levels in severe/very severe VKC compared with the mild/moderate cases. The novel finding opens up fresh targets for intervention in these refractory cases.

  • ocular surface
  • inflammation
  • biochemistry
  • conjunctiva
  • immunology

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Footnotes

  • Contributors VM: experimentation and data analysis, drafting of manuscript. GS: experimental and data analysis, manuscript editing, discussion. NA: Guarantor, concept and study design, data analysis, discussion, manuscript drafting, editing and funding. SA: study design, clinical specimen and data analysis, discussion and manuscript drafting and editing. AMA: clinical specimen. BS and GI: study design, clinical specimen and data analysis, discussion and manuscript drafting and editing. USD, ML and TV: Tear Sphingolipid Analysis by LC-MS/MS (online supplemental annexure A), data analysis.

  • Funding Funded by ICMR, Govt. of India, Project No: (5/4/6/09/OPH/15-NCD-II).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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