June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
Retinal vein occlusion causes mitochondria dysfunction leading to loss of Müller cell lateral processes and visual dysfunction.
Author Affiliations & Notes
  • Michael J Allingham
    Ophthalmology, Duke University Eye Center, Durham, North Carolina, United States
  • Nomingerel Tserentsoodol
    Ophthalmology, Duke University Eye Center, Durham, North Carolina, United States
  • Peter Saloupis
    Ophthalmology, Duke University Eye Center, Durham, North Carolina, United States
  • Scott W Cousins
    Ophthalmology, Duke University Eye Center, Durham, North Carolina, United States
  • Priyatham S Mettu
    Ophthalmology, Duke University Eye Center, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Michael Allingham, Stealth Biotherapeutics (F); Nomingerel Tserentsoodol, None; Peter Saloupis, None; Scott Cousins, Stealth Biotherapeutics (F), Stealth Biotherapeutics (C); Priyatham Mettu, Stealth Biotherapeutics (F)
  • Footnotes
    Support  NIH K08 grant 1K08EY026627
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1926. doi:
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      Michael J Allingham, Nomingerel Tserentsoodol, Peter Saloupis, Scott W Cousins, Priyatham S Mettu; Retinal vein occlusion causes mitochondria dysfunction leading to loss of Müller cell lateral processes and visual dysfunction.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1926.

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

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Abstract

Purpose : Currently, the mechanisms of visual dysfunction in macular edema are not well understood. We tested the hypothesis that Müller cell mitochondrial dysfunction contributes to visual dysfunction in mouse retinal vein occlusion, a model of retinal edema.

Methods : Retinal vein occlusion (RVO) was induced immediately following intravenous injection of rose bengal (66mg/kg) using a 532 nm wavelength laser to place 3-7 applications at 80 mW and 50 micron spot size directed at one superior and one inferior retinal vein approximately 1 disc diameter away from the nerve. Negative control consisted of placing an equal number of laser spots without targeting the retinal vein. Male and female C57BL/6J mice aged 7-9 months (Jackson Labs) with confirmed absence of Crb1rd8, GLAST-CreER and Rosa26 mTmG mice were obtained from Jackson Labs. Cre expression was induced by treating mice with tamoxifen (100mg/kg) administered intraperitonealy daily for 5 consecutive days. Elamipretide, a mitochondrial protective drug, was administered intraperitoneally (2mg/kg/day) using prevention and intervention strategies. Retinal histology and electroretinograms were evaluated on days 2 and 7 following induction of RVO. Nonparametric statistical testing was performed using JMP Pro 14 (SAS, Cary NC).

Results : RVO induced mitochondrial dysfunction in isolated retinas evidenced by increased superoxide and flavoprotein autofluorescence and this was prevented by treatment with elamipretide. RVO caused loss of Müller cell perisynaptic lateral processes in the inner and outer plexiform layers and this was associated with loss of synaptic vesicle 2 (SV2) and synaptotagmin 2 (ZNP-1) staining suggesting inner retinal synaptic dysfunction. Post-RVO ERGs demonstrated major decreases in B-wave amplitudes. Treatment with elamipretide using either intervention or prevention approaches significantly restored Müller cell lateral processes, synaptic markers and ERG B-wave amplitudes.

Conclusions : RVO causes loss of Müller cell support function which is associated with synaptic dysfunction in the inner and outer plexiform layers and visual dysfunction. Treatment with elamipretide, a mitochondria protective drug, prevents and reverses these changes. This suggests that mitochondria targeted therapy may improve vision in RVO or other diseases manifesting macular edema.

This is a 2020 ARVO Annual Meeting abstract.

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