June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Temporal and isoform-specific expression analysis of the multiuse CTBP2/RIBEYE locus in the developing chicken and human retina.
Author Affiliations & Notes
  • Ray Enke
    Biology, James Madison University College of Science and Mathematics, Harrisonburg, Virginia, United States
  • Devansh Agarwal
    Bioengineering, University of California San Diego, La Jolla, California, United States
  • Elizabeth Gage
    Biology, James Madison University College of Science and Mathematics, Harrisonburg, Virginia, United States
  • Calvin Chenault
    Biology, James Madison University College of Science and Mathematics, Harrisonburg, Virginia, United States
  • Kameron Washington-Brown
    Biology, James Madison University College of Science and Mathematics, Harrisonburg, Virginia, United States
  • Sarah Szvetecz
    Mathematics & Statistics, James Madison University College of Science and Mathematics, Harrisonburg, Virginia, United States
  • Nusrat Jahan
    Mathematics & Statistics, James Madison University College of Science and Mathematics, Harrisonburg, Virginia, United States
  • Melissa Kaye Jones
    Ophthalmology, University of California San Diego, La Jolla, California, United States
  • Donald J Zack
    Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Karl J Wahlin
    Ophthalmology, University of California San Diego, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Ray Enke None; Devansh Agarwal None; Elizabeth Gage None; Calvin Chenault None; Kameron Washington-Brown None; Sarah Szvetecz None; Nusrat Jahan None; Melissa Jones None; Donald Zack None; Karl Wahlin None
  • Footnotes
    Support  NEI R15 grant #1R15EY028725-01A1
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 496 – A0073. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ray Enke, Devansh Agarwal, Elizabeth Gage, Calvin Chenault, Kameron Washington-Brown, Sarah Szvetecz, Nusrat Jahan, Melissa Kaye Jones, Donald J Zack, Karl J Wahlin; Temporal and isoform-specific expression analysis of the multiuse CTBP2/RIBEYE locus in the developing chicken and human retina.. Invest. Ophthalmol. Vis. Sci. 2022;63(7):496 – A0073.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Complex transcriptional gene regulation allows for multifaceted isoform production during retinogenesis. Novel mRNA isoforms transcribed from a single locus can have unlimited potential to code for diverse proteins with different functions. In this study, we explored the CTBP2/RIBEYE gene locus and its unique repertoire of transcripts that are conserved among vertebrates.

Methods : We studied the transcriptional coregulator (CTBP2) and ribbon synapse specific structural protein (RIBEYE) using the developing chicken retina and developing human retinal organoid model systems, as well as in dissected post mortem adult human retina tissue. We performed comprehensive histochemical and multiomics analyses to pinpoint cell and developmental stage-specific expression of CTBP2/RIBEYE isoforms in each of these systems.

Results : We demonstrated that CTBP2 is widely expressed in retinal progenitors beginning in early retinogenesis, but becomes limited to GABAergic amacrine cells in the mature retina. Inversely, RIBEYE is initially epigenetically silenced in progenitors and later expressed in photoreceptor and bipolar cells, where they localize to ribbon synapses. Analysis of previously described ChIP-seq data suggests that differential binding of CRX and OTX2 transcription factors may play a role in isoform-specific expression patterns.

Conclusions : These analyses demonstrate that complex regulation of the multiuse CTBP2/RIBEYE locus is conserved during vertebrate retinal development. Our study also supports a mechanism for epigenetic regulation of this locus by modulating the binding of K50 homeodomain transcription factors.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 


High-resolution staining of CTBP2 and RIBEYE in the mature chick retina. Cryosectioned chicken retinas at (A,B) P3 exhibiting CTBP2 expression in the INL and GCL (diagonal arrows) as well as the IPL and OPL (vertical arrows). (B,D,F,H) Sections were counterstained with Hoechst for cell contrast. (C,D) A tri-laminar synaptic structure representing the PR projections terminating at synaptic sublayers 1–3. (E,F). CTBP2 positive nuclei in the amacrine cell layer. (G,H) Scattered nuclei in the GCL. Scale bars = 25 μm in (A), 5 μm in (C,E,G).


High-resolution staining of CTBP2 and RIBEYE in the mature chick retina. Cryosectioned chicken retinas at (A,B) P3 exhibiting CTBP2 expression in the INL and GCL (diagonal arrows) as well as the IPL and OPL (vertical arrows). (B,D,F,H) Sections were counterstained with Hoechst for cell contrast. (C,D) A tri-laminar synaptic structure representing the PR projections terminating at synaptic sublayers 1–3. (E,F). CTBP2 positive nuclei in the amacrine cell layer. (G,H) Scattered nuclei in the GCL. Scale bars = 25 μm in (A), 5 μm in (C,E,G).

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×