June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
ARL2BP, a protein linked to retinitis pigmentosa, regulates the growth of photoreceptor microtubular axonemes
Author Affiliations & Notes
  • Abigail Hayes
    Biochemsitry, West Virginia University, Morgantown, West Virginia, United States
  • Ratnesh Singh
    Biochemsitry, West Virginia University, Morgantown, West Virginia, United States
    BioTime, Alameda, California, United States
  • Visvanathan Ramamurthy
    Biochemsitry, West Virginia University, Morgantown, West Virginia, United States
    Ophthalmology, West Virginia University, Morgantown, West Virginia, United States
  • Footnotes
    Commercial Relationships   Abigail Hayes, None; Ratnesh Singh, None; Visvanathan Ramamurthy, None
  • Footnotes
    Support  R01EY025536 and R01EY017035
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 347. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Abigail Hayes, Ratnesh Singh, Visvanathan Ramamurthy; ARL2BP, a protein linked to retinitis pigmentosa, regulates the growth of photoreceptor microtubular axonemes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):347.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Blinding diseases such as retinitis pigmentosa (RP) are linked to defects in multiple ciliary proteins, including ARL2 binding protein (ARL2BP). Mutations in ARL2BP also cause situs inversus (organ reversal) in humans, a condition associated with defective cilia in the node of developing embryos. Defects in photoreceptor cilia as well as situs inversus in human patients suggest that ARL2BP plays an invaluable role in structure and function of the cilia. Using an animal model lacking ARL2BP, our goal is to understand the mechanism behind photoreceptor ciliogenesis and disc morphogenesis/organization in the outer segment (OS).

Methods : We generated a mouse knockout (KO) of ARL2BP using the Crispr-Cas9 system. Protein and mRNA levels were measured by immunoblotting and RT-PCR. Immunocytochemical staining was used to investigate the morphology of the retina and protein localization. Electroretinogram recordings (ERGs) were performed to assess photoreceptor function. Full body dissections were completed to examine organ placement. Littermates were used in all experiments as controls (n=4).

Results : ERGs revealed a progressive decline in photoreceptor responses in animals lacking ARL2BP with 50% reduction at post-natal day 16 (P16) when the retinal development, as judged by light microscopy, was normal. Immunofluorescence staining of photoreceptor cilia displayed shorter axonemes in ARL2BP KO’s as early as P10, when photoreceptor OS are still developing. Furthermore, organ reversal was present in all animals lacking ARL2BP.

Conclusions : Our animal model recapitulates the phenotype observed in ARL2BP patients. Prior to photoreceptor degeneration, we find reduced photoreceptor function and shortened axonemes. Based on these findings, we postulate that ARL2BP is involved in regulating the growth and stability of ciliary axonemes. Since photoreceptor axonemes are intimately associated with OS development, we propose that loss of ARL2BP disrupts disc organization thus affecting photoreceptor function. Currently, studies are underway to rigorously test this hypothesis using multiple models. We are also examining the length and motility of cilia present in the embryonic node in animals lacking ARL2BP. These experiments will shed light on the function of ARL2BP and ultimately contribute to our understanding of cilia development and photoreceptor structure.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

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.

×