A mouse is not just a mouse

Age-related macular degeneration (AMD) is the most common cause of vision loss and blindness in older people in the Western world.

The most aggressive form is “wet AMD”, a disease in which the formation of new blood vessels in the underlying choroid of the retina leads to fluid and swelling in the eye.

In a new study from Aarhus University that has just been published in the scientific journal Investigative ophthalmology and visual sciences (IOVS), the authors reviewed the last five years of studies in a disease model corresponding to 380 scientific articles. Research into the mechanisms behind disease – and therefore the development of new treatment modalities – is often based on laboratory animals, in which new blood vessels are artificially created in the retina, usually using of lasers.

According to a press release from the University of Aarhus, the review of numerous studies shows an imbalance in the use of laboratory animals; the researchers generally choose to use young, healthy male mice, although they know that the sex and age of the mice play a role in the degree of vessel formation.

Bjørn K. Fabian-Jessing, MD, a doctoral student and first author of the study, noted that mostly young, healthy male mice are used for research on this type of vessel formation.

“It makes sense from an ethical, financial, and time perspective, because mice are inexpensive compared to larger laboratory animals, and studies can be done relatively quickly,” he said in the University press release. “Biological variation can also be limited. However, AMD is a disease that occurs most frequently in older people, and the disease occurs just as frequently in women – perhaps even a little more frequently, when you look at “wet AMD”.

Previous studies have shown a discrepancy between the treatment effects seen in animal studies and in human clinical trials.

“We are apparently seeing a ‘translation gap,’ as the research is not taking place in the most relevant animal model,” Fabian-Jessing said in a statement. “Greater biological variation could be achieved, for example, by using more female mice and/or older animals. This would likely increase the possibility of translating the research into clinical trials – and perhaps, ultimately, reduce the number of laboratory animals, as results from preclinical animal testing would then be easier to extrapolate.

Poor reports

In addition to describing animal models, the article also focuses on the degree of notification.

“We can see that many studies do not report important variables, such as the number of mice used,” Fabian-Jessing said in the release. “This makes it difficult to compare studies and assess the value of the results. This is worrying, because it makes it impossible to reproduce the results, which reduces their reliability.

Call for better guidelines

The university’s press release noted that data in the eye field had not yet been collected and synthesized in this way.

“The new study calls for the development and updating of guidelines for these animal models,” Fabian-Jessing explained. He is supported by Professor Thomas Corydon, who is also behind the study:

“The implementation of concrete guidelines will improve the quality, value and comparability of animal testing, which will naturally be of great benefit to the research, understanding and future treatment of eye disease,” added Thomas Corydon in the communicated.

It encourages leading researchers in the field to develop consensus guidelines, as has already been done for preclinical research in other medical specialties.

Corydon explained that implementing higher methodological standards, greater biological variability within animal models, and a greater degree of relevant and detailed reporting will result in higher quality research that is more directly comparable.

“This way, the overall research field can work better in the same direction – for the benefit of patients, and perhaps with the help of fewer laboratory animals, because there will be fewer wasted experiments”, concluded Corydon.

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