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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)
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.
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.
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.
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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