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Freya M Mowat, Annie Oh, Melanie Louise Foster, Priyatham S Mettu, Scott W Cousins; Repetitive periocular delivery of hydroquinone in canines results in dysfunction of central retinal cone photoreceptors. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4555. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Cone dysfunction in the setting of dry age-related macular degeneration is challenging to model in species without a macula. We explored the susceptibility of central cones in vivo to hydroquinone, a mitochondrial toxin contained in cigarette smoke and which has been implicated in AMD pathobiology, in the canine, a species that contains a fovea-like region of cone enrichment.
Five 8-month old beagle dogs (2 females 3 males) underwent unilateral periocular injections of 1ml of 225mM hydroquinone; the contralateral eye was injected with phosphate buffered saline. Two to three rounds of five consecutive injections at 3-day intervals were performed to provide chronic exposure to the toxin. Outcome measures included in vivo imaging (optical coherence tomography, fundus and infrared photography, and autofluorescence), full-field and multifocal electroretinography, and testing of visual navigation ability. Results were compared using ANOVA.
One hydroquinone treated eye developed a focal hypofluorescent lesion affecting the area centralis after 5 injections, suspected to be associated with focal retinal pigment epithelial cell loss. The lesion increased in size after a further 5 injections. This area had focally reduced retinal function compared with surrounding areas; reduced area centralis function was also identified in all other hydroquinone treated eyes (n= 5 total) compared with contralateral saline treated eyes. Mean difference in multifocal ERG amplitude in the area centralis between hydroquinone and saline treated eyes after 10 injections was 19.49nV/deg2 (p<0.05). Retinal layer thickness in the area centralis was unffected by treatment. Full-field dark- and light-adapted electroretinography and visual navigation ability in mesopic lighting was unaffected by treatment.
The canine area centralis appears to be focally susceptible to the effects of the mitochondrial toxin, hydroquinone. This model could be utilized to study mechanisms of macular susceptibility to injury in diseases such as age-related macular degeneration.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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