June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Efficacy of tandospirone and cytokine production in the mouse blue light damage model of dry AMD.
Author Affiliations & Notes
  • Jeffrey Adam Jamison
    R&D Division, Experimentica Ltd., Forest Park, Illinois, United States
  • Anita Kirti Ghosh
    R&D Division, Experimentica Ltd., Forest Park, Illinois, United States
  • Sean David Ogle
    R&D Division, Experimentica Ltd., Forest Park, Illinois, United States
  • Nathaniel Edward Pappenhagen
    R&D Division, Experimentica Ltd., Forest Park, Illinois, United States
  • Marianna Bacellar-Galdino
    R&D Division, Experimentica Ltd., Forest Park, Illinois, United States
  • Simon Kaja
    R&D Division, Experimentica Ltd., Forest Park, Illinois, United States
    Departments of Ophthalmology and Molecular Pharmacology & Neuroscience, Loyola University Chicago, Maywood, Illinois, United States
  • Footnotes
    Commercial Relationships   Jeffrey Jamison Experimentica Ltd, Code E (Employment), AcuiSee LLC, Code O (Owner), ONL Therapeutics, Code O (Owner), AcuiSee LLC, Code P (Patent); Anita Ghosh Experimentica Ltd., K&P Scientific LLC, Code C (Consultant/Contractor), Experimentica Ltd, Code E (Employment), eyeNOS Inc, Code I (Personal Financial Interest), eyeNOS Inc, Code P (Patent), Experimentica Ltd., K&P Scientific LLC, Code R (Recipient), Experimentica Ltd., eyeNOS Inc., Code S (non-remunerative); Sean Ogle eyeNOS, Inc., Code C (Consultant/Contractor), Experimentica Ltd., Code E (Employment); Nathaniel Pappenhagen Experimentica, Ltd, Code E (Employment); Marianna Bacellar-Galdino AcuiSee LLC, Code C (Consultant/Contractor), Experimentica Ltd. , Code E (Employment); Simon Kaja Experimentica Ltd., Code C (Consultant/Contractor), Departments of Ophthalmology and Molecular Pharmacology & Neuroscience, Loyola University Chicago, Maywood, IL, USA, Code E (Employment), Experimentica Ltd., K&P Scientific LLC, Code F (Financial Support), Experimentica Ltd., K&P Scientific LLC, Code I (Personal Financial Interest), eyeNOS Inc., Code P (Patent), Experimentica Ltd., K&P Scientific LLC, Code R (Recipient), Experimentica Ltd., K&P Scientific LLC, Code S (non-remunerative)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4597 – F0389. doi:
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    • Get Citation

      Jeffrey Adam Jamison, Anita Kirti Ghosh, Sean David Ogle, Nathaniel Edward Pappenhagen, Marianna Bacellar-Galdino, Simon Kaja; Efficacy of tandospirone and cytokine production in the mouse blue light damage model of dry AMD.. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4597 – F0389.

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

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Abstract

Purpose : Blue light induced photooxidative stress (BLD) is an established model of advanced geographic atrophy observed in patients with dry AMD. 5-HT1A agonists have demonstrated neuroprotection in rat BLD studies and other mouse CNS injury models. The purpose of this work was to evaluate the 5-HT1A agonist tandospirone (tando) to provide protection in the mouse BLD model, and to measure cytokine production in the Balb/C mouse retina at 1-7 days after light exposure.

Methods : Male, 10-14 week old Balb/C mice: Group 1 daily subcutaneous injections of vehicle, 5 or 10 mg/kg tando on Day -2 to Day 2, N=5. Group 2 no treatment and were sacrificed at 1, 3 and 7 days post light exposure. N=6. Group 3 no treatment no light exposure, N=6. Group 1 and 2 animals were dark adapted overnight and on Day 0 exposed to 19-21 klux of spectrally filtered blue light for 4 hours. Prior to sacrifice all animals received electroretinograms (ERGs) to assess retinal function, and retinal damage was evaluated with OCT imaging. Eyes were collected from Group 2 and 3 and the cytokines IFNg, IL-1b, IL-2, -4, -5, -6, -10, -12p70, KC/GRO and TNFa were measured using the Mesoscale Discovery system.

Results : ERG amplitudes and retinal thickness was significantly reduced 50-70% in vehicle and the 5 mg/kg tando treated animals compared to Group 3. Animals treated with 10 mg/kg had a ~30% decrease in ERG amplitude and retinal thickness which were significantly better than vehicle treated. IL -2, -4, -12p70 and IFNg were below the lowest limit of quantification. Compared to Group 3, there was a non-significant increase of IL-5 from 1.4 to 1.7, IL-6 from 89.8 to 261.4, KC/GRO from 90.6 to 284.1 and TNFa from 62.5 to 102.7 pg/ml at Day 7 post light exposure and little change at Day 1 or Day 3. There was a non-significant decrease of IL-10 from 2.1 to 0.6 pg/ml at Day 3 post light exposure and little change at Day 1 or Day 7. There was a significant increase of IL-1b from 6.9 to 36.5 pg/ml at Day 7 post light exposure and little change at Day 1 or Day 3.

Conclusions : The 5HT1a agonist tandospirone is a viable positive control for drug discovery at 10 mg / kg in Balb/C mice. Up to 7 days post exposure the cytokines measured are insignificant other than IL-1b, which has been demonstrated to be upregulated in other models of retinal pigmented epithelial cells and photoreceptor cells damage.

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

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