Animal models of age-related macular degeneration and their translatability into the clinic

Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness in people over the age of 55. Despite its common nature, the etiology of the disease involves both genetic and environmental factors, the interaction of which is not fully understood. Animal models, including the mouse, rat, rabbit, pig and non-human primate, have been developed to study various aspects of the disease and to evaluate novel therapies; however, no single model has been developed to emulate all aspects of the disease. This review will discuss the various existing models of AMD, their strengths and limitations and examples of their use in current AMD research.

Keywords::

• age-related macular degeneration
• animal model
• mouse
• non-human primate
• pathology
• pig
• rabbit
• rat
• therapy

Financial & competing interests disclosure

The NEI Intramural Research Program supported the work. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The most popular models for age-related macular degeneration (AMD) research are genetically engineered mice, even though they do not have a macula, and have been used for increasing understanding of the pathogenic mechanisms of AMD and for screening preventative (age-related eye disease study 2 diet) and responsive therapies (sIL-17R).

• Rats, pigs and non-human primates have been used for AMD research, but primarily in the context of laser-induced CNV. Genetic models in pig (ELOVL4) and rats (OXYS) are new and have not been fully developed.

• Though non-human primates are the only current model of AMD with a macula, they may be phased out of study due to the increased costs, long experimental time frame and ethical issues.

• The pig is the next closest model in terms of retinal architecture and eye globe size; however, it is not widely applied and is still an immature model system.

• The rabbit’s merangiotic and relatively hypoxic retina makes it a poor model for AMD research, though the increased size and simple housing may make it useful in determining the pharmacokinetic and pharmacodynamics of new therapeutic compounds.

• Findings in animal models do not always perfectly translate into findings in the clinic; performing a more comprehensive and integrated evaluation of preclinical data will increase the predictive utility of animal models.Improving animal models of AMD is likely to occur as scientific understanding of AMD pathogenesis in humans is more fully elucidated. New scientific and diagnostic technologies as well as improved clinical classifications will aid greatly in this process.

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