Setup and evaluation of a model for dry age-related macular degeneration by using blue light induced retinal damage in pigmented and non-pigmented mice

Purpose:

Age-related macular degeneration (AMD) is one of the most widely spread retinal diseases worldwide in elderly people leading to visual impairment and blindness. AMD is characterized by retinal dysfunction, photoreceptor degeneration, RPE atrophy and inflammation. Further investigation of the disease stages via the blue light induced retinal degeneration model, possibly mimicking certain processes of AMD, can provide additional insights which may contribute to a better understanding, prognosis and treatment of this disease.

Methods:

Pigmented or non-pigmented mice were exposed to blue light in defined conditions to induce mild retinal degeneration. Progression of the pathology was evaluated longitudinally via spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) and electroretinography (ERG). Two compounds were administered intravitreally (IVT) or intraperitoneally (IP) in the mice and evaluated with the above mentioned methods to demonstrate efficacy and reproducibility.


Results:

Blue light induction resulted in a clear mild-to-moderate degenerative effect as observed via reduced scotopic ERG responses (a-wave, b-wave; day 4 post light induction (pLI)). Furthermore, total retina thickness was decreased as measured on OCT images (day 7 pLI) and the presence of atrophy was observed via FAF (from day 7 pLI). In the non-pigmented mice the pathology evolved to increased injury after 4 weeks, as evaluated by FAF. For pigmented eyes higher exposure show similar retinal lesions as compared to non-pigmented; consecutive sessions showed an increased damage. Administration of the compounds to the mice showed protection against retinal degeneration.

 

Conclusion:

Blue light exposure induced mild retinal morphological and functional changes. Evaluation of these alterations using non-invasive methods, showed that the setup of the blue light induced model was reproducible in 2 mouse strains. The findings that blue light causes damage that can be attenuated by candidate compounds for treating dry AMD, suggest that the model may be a useful tool in screening compounds for potential efficacy in dry AMD.

Authors

Jansen Sandra, Van Bergen Tine, Feyen Jean, Stitt Alan

Organisations

Oxurion NV

Presenting author

, , Oxurion
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