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Rabah Dabouz, Carlos José Rivera, Sylvain Chemtob; A novel IL-1 receptor modulator prevents photoreceptor loss in a model of age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4909.
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The objective of this study is to evaluate the implications of IL-1β in photoreceptor degeneration using a model of blue light in rodents.
CD-1 mice (12-16 weeks-old) were exposed to blue LED light (6000 lux at 450nm) for 1 hour and then sacrificed at day 3 post-illumination. Mice were intraperitoneally treated or not with a peptide antagonist of the IL-1β receptor, named Rytvela (or 101.10) twice per day until sacrifice. Several markers related to the inflammatory process such as F4/80, NLRP3,Caspase-1, IL-1β and Glial fibrillary acidic protein(GFAP) were evaluated by immunohistochemistry. Photoreceptor cell death was assessed by TUNEL assay and Caspase-3 immunofluorescence.
Immunofluorescence experiments revealed an infiltration of positive F4/80 cells (microglia and macrophages) into the subretinal space in mice exposed to blue light, which was significantly (p<0.) abrogated with Rytvela treatment. Co-localization of NLRP3, Caspase-1, and IL-1β with F4/80 positive cells was clearly detected in the subretinal space, suggesting that these inflammatory cells are the main source of IL-1β. Interestingly, GFAP immunoreactivity, a marker of stress in Müller cells, was augmented in retinas exposed to the blue light, and reduced with Rytvela administration. The TUNEL assay showed that Rytvela prevents photoreceptor apoptosis in the retina of mice exposed to blue light. Likewise, co-culture of retinal explants with LPS-ATP activated bone marrow-derived macrophages resulted in a high number of TUNEL positive photoreceptors, which was reduced by treatment with Rytvela.
These results show that Rytvela attenuated the inflammatory response and prevented the death of photoreceptors in a model of dry AMD. Modulation of IL-1β signaling would be a useful therapeutic avenue for dry AMD, for which no approved treatment currently exists.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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