How zebrafish helps in preclinical eye disease research

Eye diseases are a heterogeneous group of diseases affecting the eye with different causes and severity. The most common eye diseases are related to refraction errors and infections that are not severe, most of them with effective treatments available. However, as we age, chronic eye diseases, which are degenerative affections, become more common and they can cause severe vision reductions and even blindness.

Whilst research is ongoing, many chronic eye diseases cannot be reversed or cured yet. In consequence, it is mandatory to find new diagnostic and preventive tools and new therapeutic options to treat these illnesses.

In this sense, the zebrafish is proving to be a useful and reliable alternative model in the study of eye conditions and finding medicines to prevent and cure them.

How common are eye diseases?

According to the World Health Organization, 2.2 billion people worldwide suffer from visual impairment, and half of these cases could have been prevented or have not yet been reviewed. Specifically, chronic eye diseases affect hundreds of millions of people worldwide. The most common ones are the following::

Age-related macular degeneration (AMD)
Cataracts
Glaucoma
Diabetic retinopathy

Some of these deteriorating affections can also be genetically linked. For example, in the case of glaucoma, the odds of suffering the disease inside a family increase over 4-9 times when exists an already affected person on this family. Or in the case of age-related macular degeneration, where there is a 50% more probability to develop the disease inside a family that presents already an affected member.

Besides, as these age-related chronic eye diseases will be more prevalent as the global population lives longer, it is essential to fasten in the development of new therapeutic options and, specifically, in the Drug Discovery process.

retina

Zebrafish and eye disease research

Zebrafish is an important research model in the study of the prevention, treatment, and reversing of eye diseases due to their similarity to humans in eye genetics, and being a big part of their body. Also, the zebrafish is diurnal, meaning it is most active during the day and rests at night, following the circadian rhythm that the human body responds to.

In addition, they present a natural ability for eye regeneration, making them an ideal candidate for vision loss tests. This condition differs from humans as the zebrafish optic nerve can repair itself in approximately 7 days when its damaged, and humans are unable to regenerate their nerves.

This makes Zebrafish an ideal candidate for vision loss experiments and the study of vision problems linked to genetics.

Most common assays are based on monitoring the progression or even improvement of potential therapeutic drugs at various stages of different eye diseases in light and darkness conditions. This can assess how eye behavior alters as a disease progresses and how certain drugs may improve vision.

One example of these assays is the research on the human retina damaged due to a loss of photoreceptors. This is usually a result of macular degeneration and can result in a loss of peripheral or central vision, night blindness, and retina pigmentation.

Photoreceptors are light-sensitive cells in the retina that send signals to the brain. These consist of two forms of cells:

Cone cells – responsible for vision in bright light and colors
Rod cells – allowing vision in dim lighting

The retina contains 6 million cone cells and 120 million rod cells and when these become damaged eye diseases can occur. The zebrafish eye also has these cone receptors that function in the same way as those in the human eye (i.e. reaction to light).

An advantage of using zebrafish in preclinical testing (before the clinical trial stage, when drugs are tested on humans) is that they are a cost-effective, efficient model. and accounts for a multitude of benefits including:

High reproductive rate (i.e. obtained hundreds of embryos per day).
Easy scalability for Hight Content Screenings.
Fast organogenesis, being all organs functional at 5 days post-fertilization, including the nervous system.
The possibility of using larvae animals, which presents fewer ethical concerns, and is in coherence with the 3Rs principles to reduce the amount and the suffering of laboratory animals.
Transparency in the larval stage, allowing easier visual studies and good in vivo evaluations.

In consequence, preclinical assays in zebrafish are a very reliable and relevant New Approach Method (NAM) for Drug Discovery in eye diseases.

Conclusion

Chronic eye diseases are a major health concern as they are responsible for severe visual loss that can progress to blindness. Furthermore, they are diseases that are becoming more prevalent due to the aging of the population.

Therefore, it is mandatory to find new diagnostic, preventive, and therapeutic options to minimize the impact of these illnesses. In this sense, an increase in the pre-clinical research efforts in Drug Discovery is a key step to achieving these goals. Thus, zebrafish is a valuable NAM that provides a cost-effective, efficient, and highly scalable alternative to mammals with fewer ethical concerns for pre-clinical Drug Discovery.