June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Ephrin Forward Signaling as A Therapeutic Target in Hereditary Optic Neuropathy
Author Affiliations & Notes
  • Thomas Strong
    Molecular, Cell & Developmental Biology, University of Miami School of Medicine, Miami, Florida, United States
    Department of Ophthalmology, University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
  • Nicholas Kypraios
    Department of Ophthalmology, University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
  • Ronaldo Nuesi
    Department of Ophthalmology, University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
  • Ryan Alexander Gallo
    Molecular, Cell & Developmental Biology, University of Miami School of Medicine, Miami, Florida, United States
    Department of Ophthalmology, University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
  • Michelle Zhang
    Cancer Biology, University of Miami School of Medicine, Miami, Florida, United States
    Department of Ophthalmology, University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
  • Acadia Hanne Marlene Moeyersoms
    Cancer Biology, University of Miami School of Medicine, Miami, Florida, United States
    Department of Ophthalmology, University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
  • Daniel Pelaez
    Molecular, Cell & Developmental Biology, University of Miami School of Medicine, Miami, Florida, United States
    Department of Ophthalmology, University of Miami Health System Bascom Palmer Eye Institute, Miami, Florida, United States
  • Footnotes
    Commercial Relationships   Thomas Strong, None; Nicholas Kypraios, None; Ronaldo Nuesi, None; Ryan Gallo, None; Michelle Zhang, None; Acadia Moeyersoms, None; Daniel Pelaez, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2989. doi:
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      Thomas Strong, Nicholas Kypraios, Ronaldo Nuesi, Ryan Alexander Gallo, Michelle Zhang, Acadia Hanne Marlene Moeyersoms, Daniel Pelaez; Ephrin Forward Signaling as A Therapeutic Target in Hereditary Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2989.

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

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Abstract

Purpose : Optic neuropathies are a major cause of irreversible blindness worldwide. While we know many risk factors, the molecular progression towards synaptic instability, neurite retraction, and, ultimately, neuronal loss has yet to be fully elucidated. The first step in halting or reversing this progression is to identify potential molecular targets for intervention. Studies show that ephrin signaling is one of the most dysregulated signaling pathways in the pathophysiology of optic neuropathies. We hypothesize that synaptic instability, neurite retraction, and subsequent neuronal apoptosis are initiated by the anachronic reactivation of the Eph-receptor forward signaling.

Methods : To investigate the correlation between Eph-receptor reactivation and RGC loss we will use the DBA/2J (D2J) mouse model along with its genetically matched control, the DBA/2J-Gpnmb+/SjJ mouse. A semi-quantitative immunoblot-based assay to profile the phosphorylation in Eph-receptors will characterize receptor activation temporally. Immunofluorescence confocal microscopy (IF) will identify Eph-receptors localization within the inner retina, and the interplay between retina neuronal and glial compartments.

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 of 2mo and 10mo D2J retinas shows an overall increase in phosphorylation temporally in both EphA and EphB classes. Both EphA and EphB class receptors are observed to be localized within the GCL with suspected localization within the OPL and the IPL for both Eph classes.

Conclusions : These preliminary results indicate that Eph receptor activation may play a role in the neuropathic progression of hereditary optic neuropathy. These results demonstrate that Eph activation can be observed as early as 2mo of age and is localized within the inner retina, indicating their potential interactions with glial components within the retina. Together these results underscore the need to explore this 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 2021 ARVO Annual Meeting abstract.

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