June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Characterization of Ephrin Receptor Activation in Hereditary and Traumatic Optic Neuropathy Models
Author Affiliations & Notes
  • Thomas Strong
    Molecular, Cell & Developmental Biology, University of Miami Miller School of Medicine, Miami, Florida, United States
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Galina Dvoriantchikova
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Ryan Alexander Gallo
    Molecular, Cell & Developmental Biology, University of Miami Miller School of Medicine, Miami, Florida, United States
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Ronaldo Nuesi
    Florida International University Herbert Wertheim College of Medicine, Miami, Florida, United States
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Michelle G Zhang
    The Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami, Miller School of Medicine, Miami, Florida, United States
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
  • John Yohan Lee
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Haley McCarthy-Levy
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Ravi Doddapaneni
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Daniel Pelaez
    Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, Florida, United States
    Molecular, Cell & Developmental Biology, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Footnotes
    Commercial Relationships   Thomas Strong, None; Galina Dvoriantchikova, None; Ryan Gallo, None; Ronaldo Nuesi, None; Michelle Zhang, None; John Lee, None; Haley McCarthy-Levy, None; Ravi Doddapaneni, None; Daniel Pelaez, None
  • Footnotes
    Support  National Eye Institute Center Grant P30EY014801, RPB Unrestricted Grant to Bascom Palmer Eye Institute
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 677. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Thomas Strong, Galina Dvoriantchikova, Ryan Alexander Gallo, Ronaldo Nuesi, Michelle G Zhang, John Yohan Lee, Haley McCarthy-Levy, Ravi Doddapaneni, Daniel Pelaez; Characterization of Ephrin Receptor Activation in Hereditary and Traumatic Optic Neuropathy Models. Invest. Ophthalmol. Vis. Sci. 2020;61(7):677.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Optic neuropathies are a major cause of irreversible blindness worldwide. While risk factors are known, the molecular progression that ultimately leads to neuronal apoptosis and blindness has yet to be fully elucidated. Recent studies show ephrin signaling as one of the most dysregulated signaling pathways in the pathophysiology of optic neuropathies. In this study, we hypothesize that neuropathic progression is initiated in part by the anachronic reactivation of repulsive ephrin forward signaling within the neural retina.

Methods : We used two optic neuropathic models, DBA/2J (D2J) mice which develop hereditary glaucomatous defects and the optic nerve crush (ONC) model in C57BL/6 (C57) mice. A semi-quantitative microarray-based assay to profile the phosphorylation of Eph receptors was then used to assay activation of several Eph receptors in a temporal manner in the D2J mice (2mo – 23mo) and ONC mice (4- and 48-hr post-injury). Immunofluorescent (IF) staining was used to confirm the localization of the activated Eph receptors within the retina.

Results : Our results show an age-dependent increase in the activation of several Eph receptors in the retina of D2J mice, with the majority of Eph receptors present in a hyperphosphorylated state at age 23mo. Interestingly, results show that EphA1, EphA3, EphA6, EphA7, EphB1, EphB2, and EphB6, are significantly phosphorylated as early as 2mo of age (p=<0.05). IF images determined the localization of Eph receptors to the RGC layer. IF analysis further showed that D2J retinas exhibit an age-dependent activation of the EphB1 and B2 receptors throughout the inner retina. IF imaging of the ONC mice shows that Eph-receptor EphA2, A3, A4, B1, and B2 become hyperphosphorylated shortly after injury (4hr) and that their spatial distribution is predominately in the inner retina.

Conclusions : These results indicate that Eph receptor activation and repulsive forward signaling may play a role in the neuropathic progression of both hereditary and traumatic optic neuropathy. These results demonstrate that Eph activation can be observed as early as 2mo of age in hereditary optic neuropathy and 4hr in traumatic optic neuropathy. Together these studies underscore the need to explore this repulsive pathway in early optic neuropathies and it provides a glimpse of the number of receptors that are present in the retina of mice and which are engaged in neuropathic states.

This is a 2020 ARVO Annual Meeting abstract.

×
×

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.

×