Article

Variables in models can provide invaluable insights to disease

There is value in studying a model of human disease that is not a carbon copy, said Jayakrishna Ambati, MD, associate professor, School of Medicine, and vice chairman, Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington.

There is value in studying a model of human disease that is not a carbon copy, said Jayakrishna Ambati, MD, associate professor, School of Medicine, and vice chairman, Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington.

Dr. Ambati defended animal models of age-related macular degeneration despite differences in eye structure and disease development between humans and other species often used in testing, such as primates, mice, and rabbits.

"Even imperfect models can provide invaluable insights," he said.

The validity of an animal model can be measured by several variables: face validity, or how well it copies the human condition; whether it obeys the genetic aspects of the disease; and how well it parallels the immunologic and pathogenetic mechanisms.

"This betrays the clinician's bias, but what is most important is how well it tells us something we didn't already know," Dr. Ambati said. "What does it predict, either about mechanisms or about treatment or diagnosis? Does it ultimately reveal some novel insights?"

He added that there is no single best choice of a model but that ongoing dialogue between basic scientists and clinical investigators will continue to lead to new discoveries.

He added that although mice lack maculas, several important insights have been gained from mouse models recently on issues such as development of choroidal neovascularization via substances found in drusen.

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