July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Knockout of zebrafish stra6 and rbp4 leads to retinal degeneration phenotypes
Author Affiliations & Notes
  • Ross F Collery
    Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Ross Collery, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4944. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ross F Collery; Knockout of zebrafish stra6 and rbp4 leads to retinal degeneration phenotypes. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4944. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Mutations in the transmembrane transporter and receptor STRA6 cause Matthew-Wood syndrome in humans, characterized by microphthalmia-anophthalmia, heart defects and diaphragmatic hernia. STRA6 acts as the only known receptor for RBP4-retinol, and facilitates bidirectional transport of retinol into the retinal pigment epithelium from circulating blood. Additionally, STRA6 activates the JAK/STAT pathway in response to RBP4-retinol binding. Inactivation of Stra6 in mouse leads to a reduction in ocular retinoids, with decreased eye size, reduced numbers of cone photoreceptors and shortened rods. Knockout of stra6 and/or rbp4 in a cone-rich diurnal animal model will provide valuable insight into requirements for retinol in the visually cone-dominant human retina.

Methods : Here we inactivate the zebrafish stra6 gene using CRISPR/Cas9 methods to delete the entire coding region, preventing any possibility of protein production. We also inactivated zebrafish rbp4 using similar methods. Wild-type and mutant zebrafish were examined as larvae and adults using in vivo spectral domain-optical coherence tomography combined with immunohistochemistry.

Results : We demonstrate that stra6 mutant zebrafish are viable, and show decreased eye size, retinal thinning and photoreceptor abnormalities. We also see that in zebrafish rbp4 mutants, photoreceptors are also compromised, but with notable differences from stra6 mutants.

Conclusions : We will carry out experiments to test the molecular profiles of eye tissues in stra6, rbp4 and double knockout lines to better understand the overlapping and non-overlapping pathways that are compromised in these retinal degeneration models.

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

×
×

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.

×