Functional and Anatomical Characterization of Atrophic Age-Related Macular Degeneration in an Aged Mouse Model

Author(s): Stéphan Tobalem, Mateusz Kecik, Maëllie Midroit, Djehna Scaldino, Sébastien Tardy, Thais Bascuas, Nina Harmening, Leonardo Scapozza, Gabriele Thumann, Martina Kropp

Purpose: To develop an animal model of atrophic age-related macular degeneration (aAMD) in aged mice that more closely mimics the natural progression of the disease. Methods: 12- and 18-month-old CBl57/6JRj mice were immunized with murine serum albumin (MSA) conjugated with carboxyethyl pyrrole (CEP). The immunization, given into the hock, was followed by 3 booster injections into the neck over a 3-month period. Immunized mice and age-matched controls were trained for a visual discrimination and an optokinetic response task to determine the objective visual threshold (OVT) at arrival and at 3 months; funduscopy and ocular coherence tomography were performed. After sacrifice, the eyes were enucleated for histological, immunofluorescent and electron microscopy analyses. Results: Retinal imaging confirmed that all mice had normal retinas upon arrival. Three months after mice were immunized the normal retinal age-related alterations were significantly more pronounced in CEP-immunized than in control mice as evidenced by drusenoid alterations, increased retinal thickness, immune activation, signs of retinal degeneration, decreased OVT. Electron microscopy indicated degeneration of the retinal pigment epithelium (RPE). Conclusions: The retinal and behavioral changes in the aged CEP-immunized mice will be useful for the investigation of novel treatments of aAMD. Translational relevance: The enhanced Aged-CEP-Mouse model enables the generation of results highly transferable to human patients and promotes the development of efficient, safe AMD therapies.

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