July 2018
Volume 59, Issue 9
ARVO Annual Meeting Abstract  |   July 2018
Circadian and dopamine modulation of sensitivity to light-induced retinal degeneration (LIRD) in mice
Author Affiliations & Notes
  • Polina Lyuboslavsky
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jana T Sellers
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Gianluca Tosini
    Pharmacology, Morehouse School of Medicine, Atlanta, Georgia, United States
  • P. Michael Iuvone
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Polina Lyuboslavsky, None; Jana Sellers, None; Gianluca Tosini, None; P. Michael Iuvone, None
  • Footnotes
    Support  NIH grants R01 EY004864 (PMI); P30 EY006360 (PMI); R01EY026291 (GT); Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5045. doi:
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      Polina Lyuboslavsky, Jana T Sellers, Gianluca Tosini, P. Michael Iuvone; Circadian and dopamine modulation of sensitivity to light-induced retinal degeneration (LIRD) in mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5045.

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

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Purpose : To test the hypothesis that the sensitivity to LIRD is modulated by circadian clocks and by dopamine D4 receptors, we examined the effects of bright light exposure at various times during the subjective day and subjective night in wild type mice and mice with targeted deletion of the Drd4 gene.

Methods : All mice were on a pigmented C3H/f+/+ background and were housed on 12 h light / 12 h dark cycle. Mice were kept in total darkness the day prior to initiating light damage. Pupils were dilated under dim red light. Thirty minutes later they were exposed to 3000 lux for 3 hours at subjective dawn, in the middle of the subjective day, at subjective dusk, and in the middle of subjective night. Controls were dilated and kept in the same room in dim light (< 50 lux). Dark-adapted ERG recordings and SD-OCT measurements were performed 3-4 weeks after bright light treatment. Eyes were fixed with glutaraldehyde, embedded in plastic, and sectioned at 5 µm for counting photoreceptor nuclei.

Results : In wild type mice, a circadian rhythm of sensitivity to LIRD was observed. Sensitivity was highest when bright light was applied at subjective dusk and subjective midnight. ERG a-wave amplitudes were significantly reduced by LIRD initiated at subjective dusk (p=0.012). Bright light at subjective midnight showed a similar trend for reduction (p<0.07). Bright light initiated at subjective dawn and midday had no significant effect on a-wave amplitudes. Similarly, SD-OCT measurement of photoreceptor layer thickness showed a significant reduction when LIRD was initiated during the subjective night (p<0.05), but not during the subjective day. Compared to the dim light control, the greatest loss in photoreceptor nuclei was observed when bright light was initiated at subjective midnight (p=0.001). A similar trend was observed in Drd4-/- mice. However, the reduction in photoreceptor layer thickness and viability was greater in Drd4-/- mice to compared to wild type controls (p<0.05), especially when light damage was initiated at subjective midnight (p<0.001).

Conclusions : The data support the hypothesis that sensitivity to LIRD is controlled in a circadian fashion and that dopamine, acting through dopamine D4 receptors, decreases the sensitivity to light-induced photoreceptor degeneration. The results also indicate that dopamine D4 receptor signaling is not driving the circadian rhythm of LIRD sensitivity.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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