July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Depth perception deficit in Rbfox1 knockout animals is associated with the downregulation of Vamp1 and Vamp2
Author Affiliations & Notes
  • Lei Gu
    Ophthalmology, University of California Los Angeles, Los Angeles, California, United States
  • Joseph Caprioli
    Ophthalmology, University of California Los Angeles, Los Angeles, California, United States
  • Natik Piri
    Ophthalmology, University of California Los Angeles, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Lei Gu, None; Joseph Caprioli, None; Natik Piri, None
  • Footnotes
    Support  Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2356. doi:
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    • Get Citation

      Lei Gu, Joseph Caprioli, Natik Piri; Depth perception deficit in Rbfox1 knockout animals is associated with the downregulation of Vamp1 and Vamp2. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2356.

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

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Abstract

Purpose : We showed earlier that Rbfox1, a regulator of alternative splicing, mRNA stability and translation, is expressed in all types of retinal ganglion cells (RGCs) as well as in subsets of amacrine cells (ACs) within the inner nuclear and ganglion cell layers. Conditional deletion of the Rbfox1 resulted in depth perception deficit. Here we present the results of transcriptome analysis of Rbfox1 KO retinas with aim to identify genes that may be responsible for visual dysfunction in these animals.

Methods : RNA sequencing (RNA-seq) was performed on retinal RNA from Rbfox1 KO (n=3) and control animals (n=3) using an Illumina HiSeq4000 sequencer at 75bp-paired-end sequencing, yielding between 49 and 78 million reads per sample. Differential expression analysis was conducted with R-project and the Bioconductor package edgeR. Statistical significance of the differential expression was determined at false discovery rate (FDR) <0.1. The Functional Annotation Tool of the DAVID Bioinformatics Resources 6.8 was used to analyze RNA-seq data with focus on genes that are known to have neuron-specific functions and KEGG DISEASE Database was used to identify genes associated with various forms of neurological conditions.

Results : Among the relatively small number of top rated differentially regulated genes, there were at least 35 genes that have been shown to have neuron-specific functions or associate with various neurological diseases, including Vamp1, Vamp2, Snap25, Trak2 and Slc1A7. Vamp1, Vamp2 and Snap25 together with syntaxins and synaptotagmin form the core of the SNARE complex that mediates synaptic vesicle fusion. Real-time PCR and immunohistochemistry confirmed the downregulation of Vamp1 and Vamp2 observed by RNA-seq. Vamp2 was abundantly expressed in the retinal inner and outer plexiform layers, whereas Vamp1 was restricted to somas and their dendrites in a subset of cells in the GCL. Colocalization with Rbpms, an RGC marker, and quantitative analysis in whole mount retinas showed that Vamp1 is expressed in approximately 8% of RGC.

Conclusions : Transcriptome analysis of Rbfox1 KO retinas identified several proteins involved in synaptic transmission, including Vamp1 and Vamp2, suggesting a role of Rbfox1 in regulation of genes important in establishing and maintaining the neural circuitry between RGCs and ACs.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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