July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
PRPF31 deficiency implicates key genes and pathways of photo-transduction as its tissue specific role (Proof-of-concept mechanism study in an ex-vivo model of RP11)
Author Affiliations & Notes
  • Narsis Daftarian
    Ophthalmology, Ocular Tissue Engineering Research Center, Tehran, Tehran, Iran (the Islamic Republic of)
    Ophthalmology, Ophthalmic Research Center, Tehran, Tehran, Iran (the Islamic Republic of)
  • Leila Azizzadeh Pormehr
    Biochemistry and Biophysics, Biochemistry and Biophysics, Dept. of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Tehran, Iran (the Islamic Republic of)
  • Shahin Ahmadian
    Biochemistry and Biophysics, Biochemistry and Biophysics, Dept. of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Tehran, Iran (the Islamic Republic of)
  • Carlo Rivolta
    Medical Genetics, Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
  • Seyed Ahmad Mousavi
    Department of stem cells and developmental biology, Cell science research center, Royan institute for stem cell biology and technology, ACECR,, Tehran, Iran (the Islamic Republic of)
  • Mozhgan Rezaeikanavi
    Ophthalmology, Ocular Tissue Engineering Research Center, Tehran, Tehran, Iran (the Islamic Republic of)
  • Hamid Ahmadieh
    Ophthalmology, Ophthalmic Research Center, Tehran, Tehran, Iran (the Islamic Republic of)
  • Footnotes
    Commercial Relationships   Narsis Daftarian, None; Leila Azizzadeh Pormehr, None; Shahin Ahmadian, None; Carlo Rivolta, None; Seyed Ahmad Mousavi, None; Mozhgan Rezaeikanavi, None; Hamid Ahmadieh, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2327. doi:https://doi.org/
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      Narsis Daftarian, Leila Azizzadeh Pormehr, Shahin Ahmadian, Carlo Rivolta, Seyed Ahmad Mousavi, Mozhgan Rezaeikanavi, Hamid Ahmadieh; PRPF31 deficiency implicates key genes and pathways of photo-transduction as its tissue specific role (Proof-of-concept mechanism study in an ex-vivo model of RP11). Invest. Ophthalmol. Vis. Sci. 2018;59(9):2327. doi: https://doi.org/.

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

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Abstract

Purpose : How PRPF31 haplo-insufficiency, as a general splicing factor is associated with retina specific disease, remains unclear. In this study, we investigated the functional splicing effects of PRPF31 downregulation in a model of Human Organotypic Retinal Culture using RNA sequencing technique.

Methods : Human eyes from young donors (20-40 years old) were obtained within the 24 hours post mortem from Iranian eye bank in compliance with the Declaration of Helsinki. The retinas were isolated and transfected using PRPF31 and scramble siRNA. PRPF31 down regulation was confirmed by quantitative real time PCR (QRT-PCR). The mRNA libraries were paired-end sequenced on Illumina HiSeq 4000 and subsequently analyzed using bioinformatics tools. QRT-PCR for some selected down-regulated genes performed to double check the results.

Results : PRPF31 depletion in siRNA treated samples led to down-regulation of 2% of genes and up-regulation of 1.5% of genes, as a whole. These differentially down-regulated genes are enriched to photo-transduction pathway (RHO, GUCA, PDEG, SAG). In addition, enrichment analysis for gene ontology revealed ATP-sensitive potassium channel complex and rhodopsin mediated signaling pathways involvement. Interestingly, transcription-coupled splicing is significantly increased in PRPF31 depleted samples, suggesting a compensatory mechanism for splicing reduction. RNA sequencing analysis confirmed by QRT-PCR results of selected genes involved in photo-transduction.

Conclusions : Our data reveals PRPF31 deficiency has a crucial role in retina specific pathology by affecting the expression of wide range of genes implicated in photo-transduction and rhodopsin mediated signaling pathway, as its major splicing function.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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