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Wennan Lu, Nestor Gomez, Jason C Lim, Alan M Laties, Claire H Mitchell; Chloroquine retinopathy as a modern model of macular degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4218.
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The lack of appropriate models for age-related macular degeneration (AMD) limits the field. Chloroquine retinopathy, also known as Bull's eye maculopathy, is associated with considerable lipid accumulations in and around RPE cells, a loss of photoreceptors and impaired vision. While the disease shares many morphological similarities with AMD, it is unknown whether chloroquine induces the biochemical or molecular markers of oxidative stress that have been linked to the disease. We have thus developed in vivo and in vitro models of chloroquine retinopathy to investigate additional parallels with AMD.
Mouse chloroquine retinopathy was induced by injecting chloroquine (50mg/kg) intraperitoneally into 3-month old C57BL/6J mice 3x/week for 6 weeks. Retinas were analyzed using protein immunoblot, ELISA, qPCR and histochemical examination. BODIPY 493/503 staining was used to evaluate accumulation of neutral lipids in Bruch's membrane. Assays were also performed on ARPE cells fed with photoreceptor outer segments (POS) and treated with chloroquine.<br />
Mice treated with chloroquine showed an increase in the lipids surrounding Bruch’s membrane compared to untreated mice, an increase in SOD2 mRNA and an increase in HNE-adducted proteins in the RPE/choroid. Increased TUNEL staining was also detected in the photoreceptors of chloroquine-treated mice. The addition of chloroquine to POS-treaded ARPE cells increased the levels of retained opsin levels, consistent with impaired degradation. Levels of oxidized lipids and of HNE-adducted proteins were also increased in chloroquine treated cells.<br />
These data demonstrate that murine and cellular models of chloroquine retinopathy demonstrate elevations in oxidative stress markers associated with age-related macular degeneration.<br />
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