June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Retinal Characterization of Sphingosine-1-Phosphate Receptor 2 Knockout Mice
Author Affiliations & Notes
  • Richard Grambergs
    The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Abhishek P. Shrestha
    The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Koushik Mondal
    The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • TJ Hollingsworth
    The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • David M. Sherry
    The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Thirumalani Vaithianathan
    The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Nawajes A Mandal
    The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Richard Grambergs None; Abhishek Shrestha None; Koushik Mondal None; TJ Hollingsworth None; David Sherry None; Thirumalani Vaithianathan None; Nawajes Mandal None
  • Footnotes
    Support  NIH EY022071, NIH EY031316, VA IO1BX004893
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1911 – A0057. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Richard Grambergs, Abhishek P. Shrestha, Koushik Mondal, TJ Hollingsworth, David M. Sherry, Thirumalani Vaithianathan, Nawajes A Mandal; Retinal Characterization of Sphingosine-1-Phosphate Receptor 2 Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1911 – A0057.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts through G protein-coupled S1P receptors (S1PR1-5) to participate in a variety of signaling pathways, but its role in the neural retina has not been studied extensively. We previously showed that S1PR2 is expressed in mouse and rat retinas, primarily in photoreceptors and bipolar cells, and expression is altered by conditions of retinal stress. In this study, we developed S1PR2 knockout (KO) mice on an albino background and performed structural and functional characterizations of their retinas under normal conditions and after intense light-induced retinal degeneration (LIRD) treatment.

Methods : Albino S1PR2 KO and wild-type (WT) littermate mice were raised under similar conditions and underwent retinal assessments at various matched age-points between 3 and 6 months. Retinal function was assessed by electroretinography (ERG), and structural differences by electron microscopy (EM) and optical coherence tomography (OCT). Immunohistochemical (IHC) labeling was used to visualize differences in neuronal and synaptic markers in light- and dark-adapted mice. Mice underwent similar assessments after LIRD (1500 lux for 6 hours) to evaluate their sensitivity to retinal stress.

Results : We found significantly elevated A- and B-wave responses at ERG flash intensities between 4-2000 cd.s/m2 in S1PR2 KO mice compared to WT at baseline (n = 12 and n = 8, respectively) and after LIRD (n = 10 and n = 11; P < 0.05). OCT further showed that KO mice (n = 8) had significantly increased retinal nerve fiber layer (RNFL) (14.8 ± 0.3µm vs 13.3 ± 0.5µm) and outer plexiform layer (OPL) (12.5 ± 0.4µm vs 11.6 ± 0.2µm) thickness compared to WT (n = 10; mean ± SE; P < 0.05). EM likewise showed differences in inner neuronal layers and OPL, and reduced synapses between rod terminal and bipolar cells in KO mice. IHC also showed differential labeling of synaptic markers and dendritic arborization of secondary neurons in KO mice compared to WT.

Conclusions : Our findings show that S1PR2 knockout alters murine retinal structural and functional characteristics, suggesting an important role of S1PR2 in the mammalian retina.

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

×
×

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.

×