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Clin Proteomics. 2017 Apr 24;14:13. doi: 10.1186/s12014-017-9148-y. eCollection 2017.

Proteomic profiling of human intraschisis cavity fluid.

Clinical proteomics

Dhandayuthapani Sudha, Mahdokht Kohansal-Nodehi, Purnima Kovuri, Srikanth Srinivas Manda, Srividya Neriyanuri, Lingam Gopal, Pramod Bhende, Subbulakshmi Chidambaram, Jayamuruga Pandian Arunachalam

Affiliations

  1. SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
  2. School of Biotechnology, SASTRA University, Thanjavur, India.
  3. Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  4. Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India.
  5. Institute of Bioinformatics, Bengaluru, India.
  6. Elite School of Optometry, Unit of Medical Research Foundation, Chennai, India.
  7. Shri Bhagwan Mahavir Vitreo-Retinal Services, Medical Research Foundation, Chennai, India.
  8. Central Inter-Disciplinary Research Facility (CIDRF), Sri Balaji Vidyapeeth Medical University, Mahatma Gandhi Medical College and Research Institute Campus, Puducherry, India.

PMID: 28450823 PMCID: PMC5404285 DOI: 10.1186/s12014-017-9148-y

Abstract

BACKGROUND: X-linked retinoschisis (XLRS) is a vitreoretinal degenerative disorder causing vision deterioration, due to structural defects in retina. The hallmark of this disease includes radial streaks arising from the fovea and splitting of inner retinal layers (schisis). Although these retinal changes are attributed to mutations in the retinoschisin gene, schisis is also observed in patients who do not carry mutations. In addition, the origin of intraschisis fluid, the triggering point of schisis formation and its progression are largely unknown still. So far, there is no report on the complete proteomic analysis of this fluid. Schisis fluid proteome could reflect biochemical changes in the disease condition, helping in better understanding and management of retinoschisis. Therefore it was of interest to investigate the intraschisis fluid proteome using high-resolution mass spectrometry.

METHODS: Two male XLRS patients (aged 4 and 40 years) underwent clinical and genetic evaluation followed by surgical extraction of intraschisis fluids. The two fluid samples were resolved on a SDS-PAGE and the processed peptides were analyzed by Q-Exactive plus hybrid quadrupole-Orbitrap mass spectrometry. Functional annotation of the identified proteins was performed using Ingenuity pathway analysis software.

RESULTS: Mass spectrometry analysis detected 770 nonredundant proteins in the intraschisis fluid. Retinol dehydrogenase 14 was found to be abundant in the schisis fluid. Gene ontology based analysis indicated that 19% of the intraschisis fluid proteins were localized to the extracellular matrix and 15% of the proteins were involved in signal transduction. Functional annotation identified three primary canonical pathways to be associated with the schisis fluid proteome viz., LXR/RXR activation, complement system and acute phase response signalling, which are involved in immune and inflammatory responses. Collectively, our results show that intraschisis fluid comprises specific inflammatory proteins which highly reflect the disease environment.

CONCLUSION: Based on our study, it is suggested that inflammation might play a key role in the pathogenesis of XLRS. To our knowledge, this is the first report describing the complete proteome of intraschisis fluid, which could serve as a template for future research and facilitate the development of therapeutic modalities for XLRS.

Keywords: Immune response; Inflammation; Intraschisis fluid; Pathway analysis; Proteome; X-linked retinoschisis

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