June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Novel flavonoid-based eye drops for the treatment of retinal degeneration
Author Affiliations & Notes
  • Ifat Sher-Rosenthal
    Goldschleger Eye Institute, Sheba Medical Center at Tel Hashomer, Tel Hashomer, Israel
    Goldschleger Eye Institute, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel
  • Ettel Bubis
    Goldschleger Eye Institute, Sheba Medical Center at Tel Hashomer, Tel Hashomer, Israel
    Goldschleger Eye Institute, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel
  • Zehavit Goldberg
    Goldschleger Eye Institute, Sheba Medical Center at Tel Hashomer, Tel Hashomer, Israel
    Goldschleger Eye Institute, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel
  • Mohamed Samara
    The Interinstitutional Analytical Instrumentation Unit, Agricultural Research Organization Volcani Center, Bet-Dagan, Israel
  • Anat Elmann
    Department of Food science Agricultural Research Organization, Agricultural Research Organization Volcani Center, Bet-Dagan, Israel
  • Ygal Rotenstreich
    Goldschleger Eye Institute, Sheba Medical Center at Tel Hashomer, Tel Hashomer, Israel
    Goldschleger Eye Institute, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel
  • Footnotes
    Commercial Relationships   Ifat Sher-Rosenthal, Sheba Medical Center (P); Ettel Bubis, None; Zehavit Goldberg, None; Mohamed Samara, None; Anat Elmann, Agricultural Research Organization (P); Ygal Rotenstreich, Sheba Medical Center (P)
  • Footnotes
    Support  Israel Innovation Authority Research Grant (Kamin-Yeda)
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3067. doi:
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    • Get Citation

      Ifat Sher-Rosenthal, Ettel Bubis, Zehavit Goldberg, Mohamed Samara, Anat Elmann, Ygal Rotenstreich; Novel flavonoid-based eye drops for the treatment of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3067.

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

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Abstract

Purpose : To assess the safety and efficacy of a novel flavonoid (TTF)- based eye drops formulation for retinal degeneration treatment.

Methods : Eye cups of 21 day-old RPE65/rd12 mice were incubated in media supplemented with 8nM TTF or the same volume of vehicle solution for 18 hours. Sections were stained with antibodies directed against cone opsins and counter-stained with DAPI. The number of positively stained cells/mm retina was recorded. Rabbits were treated with TTF eye drops and TTF concentration in anterior chamber tap removed at 5, 45, and 180 minutes was determined by HPLC to determine corneal permeability. RPE65/rd12 mice were treated twice daily, 6 days/week, for 12 weeks with eye drops containing either TTF (12.5mg/ml, n=16) or vehicle (n=16). RPE /retina flat mounts were stained with Iba-I to assess microglial activation and retinal sections were stained with TUNEL to assess treatment effect on photoreceptor apoptosis. Retinal function was determined by electroretinogram (ERG).

Results : Supplementation of 8nM TTF rescued cones photoreceptors from degeneration in the eye cups cultures in vitro. TTF penetrated the corneal barrier in rabbit eyes. The maximal concentration of TTF in anterior chamber taps was 1.7 μM, 45 minutes following eye drops instillation. Three-week treatment with TTF eye drops significantly reduced microglial activation and migration into the sub retina compared to vehicle (mean ± SD: 42±14 microglia cells/retina vs. 143 ± 28 microglia cells/retina, p=0.0063). The number of TUNEL positive cells in the photoreceptor layer was significantly lower in treated mice compared with control (mean ± SE: 2 ± 0.4 apoptotic cells/mm retina vs. 6 ± 0.8 apoptotic cells/mm, p=0.0013). A significantly higher scotopic ERG a-wave was recorded in treated mice 3 weeks following treatment initiation (p=0.005).

Conclusions : TTF eye drops may present a novel simple treatment for retinal degeneration, reducing microglial activation and inflammation, preventing photoreceptor cell death, and preserving retinal function in a mouse model of RP. No side effects were observed following 12 weeks of daily treatment with the TTF eye drops, supporting the potential feasibility for clinical application as a treatment for incurable blinding diseases.

This is a 2021 ARVO Annual Meeting abstract.

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