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
Affiliations
- SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
- School of Biotechnology, SASTRA University, Thanjavur, India.
- Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India.
- Institute of Bioinformatics, Bengaluru, India.
- Elite School of Optometry, Unit of Medical Research Foundation, Chennai, India.
- Shri Bhagwan Mahavir Vitreo-Retinal Services, Medical Research Foundation, Chennai, India.
- 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
References
- Mediators Inflamm. 2016;2016:1313027 - PubMed
- Nat Genet. 2002 May;31(1):79-83 - PubMed
- Nat Rev Mol Cell Biol. 2012 Mar 14;13(4):213-24 - PubMed
- Am J Hum Genet. 2008 Nov;83(5):572-81 - PubMed
- Mol Vis. 2009;15:833-43 - PubMed
- Clin Proteomics. 2014 Jul 14;11(1):29 - PubMed
- Retina. 2006 Sep;26(7 Suppl):S57-60 - PubMed
- Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13878-83 - PubMed
- Invest Ophthalmol Vis Sci. 2005 Jan;46(1):349-57 - PubMed
- Proteomics. 2015 Feb;15(4):836-40 - PubMed
- J Biol Chem. 2002 Nov 22;277(47):45537-46 - PubMed
- Doc Ophthalmol. 2009 Feb;118(1):69-77 - PubMed
- Cell Tissue Res. 2011 Jan;343(1):227-35 - PubMed
- Br J Ophthalmol. 1995 Jul;79(7):697-702 - PubMed
- Biochem Soc Trans. 1996 Aug;24(3):893-6 - PubMed
- Hum Mol Genet. 2002 Jun 1;11(12):1465-75 - PubMed
- Nat Genet. 1999 Jun;22(2):188-91 - PubMed
- Ophthalmol Eye Dis. 2010 Mar 11;1:23-41 - PubMed
- Nat Genet. 1997 Oct;17 (2):164-70 - PubMed
- Tumour Biol. 2016 Apr;37(4):5165-70 - PubMed
- Proteome Sci. 2013 May 20;11(1):22 - PubMed
- J Lipid Res. 2013 Jul;54(7):1744-60 - PubMed
- Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1691-5 - PubMed
- Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7036-42 - PubMed
- Mol Immunol. 2007 Sep;44(16):3901-8 - PubMed
- Eur J Ophthalmol. 2008 Sep-Oct;18(5):787-91 - PubMed
- Hum Mutat. 2010 Nov;31(11):1251-60 - PubMed
- Immunobiology. 2012 Feb;217(2):127-46 - PubMed
- Hum Mol Genet. 2002 Nov 15;11(24):3097-105 - PubMed
- Cell Death Differ. 2004 Dec;11 Suppl 2:S126-43 - PubMed
- Invest Ophthalmol Vis Sci. 2007 Feb;48(2):891-900 - PubMed
- Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18928-33 - PubMed
- Diabetologia. 1992 Mar;35(3):261-6 - PubMed
- Proteomics. 2015 Aug;15(15):2597-601 - PubMed
- J Biol Chem. 2005 Mar 18;280(11):10721-30 - PubMed
- Nat Genet. 2002 May;31(1):74-8 - PubMed
- Invest Ophthalmol Vis Sci. 2001 Mar;42(3):816-25 - PubMed
- Arch Neurol. 2000 Oct;57(10):1439-43 - PubMed
- Am J Hum Genet. 2011 Mar 11;88(3):306-16 - PubMed
- PLoS One. 2013 Jun 03;8(6):e63313 - PubMed
- Am J Hum Genet. 2004 Oct;75(4):639-46 - PubMed
- Neurobiol Aging. 2014 Jun;35(6):1510.e7-18 - PubMed
- Proteomics. 2013 Aug;13(16):2500-11 - PubMed
- Diabetes. 2004 Jun;53(6):1592-8 - PubMed
- Nihon Geka Gakkai Zasshi. 1992 Sep;93(9):968-71 - PubMed
- Am J Hum Genet. 2011 Apr 8;88(4):422-32 - PubMed
- J Zhejiang Univ Sci B. 2005 Nov;6(11):1045-56 - PubMed
- Diabetes. 1994 Mar;43(3):357-68 - PubMed
- Protein Pept Lett. 2002 Jun;9(3):211-23 - PubMed
- Proteomics. 2016 Oct;16(19):2592-2596 - PubMed
- Retina. 2007 Oct;27(8):1086-9 - PubMed
- J Biol Chem. 2005 Mar 4;280(9):7427-34 - PubMed
- N Engl J Med. 1999 Feb 11;340(6):448-54 - PubMed
- Sci Transl Med. 2015 Jul 22;7(297):297ra116 - PubMed
- Arch Ophthalmol. 2000 Aug;118(8):1098-104 - PubMed
- Nat Genet. 2001 Sep;29(1):66-9 - PubMed
- Proteomics. 2016 Apr;16(7):1146-53 - PubMed
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