Understanding the biology of vision by developing new methods for monitoring eye movements in zebrafish

Open Research Europe presents an interview with Alicia Gomez Sanchez and Yolanda Alvarez, two of the co-authors of ‘Affordable and effective optokinetic response methods to assess visual acuity and contrast sensitivity in larval to juvenile zebrafish’ in this month’s Research Spotlight.  

How would you summarize your Method Article? 

The optokinetic response (OKR) is a slow horizontal eye movement tracking an object followed by a fast movement in the opposite direction. This innate response occurs in vertebrates, including fish and mammals, from very early in life (5 days for zebrafish larvae and 6 months for human babies). 

OKR allows the eye to follow objects in motion when the head remains stationary (e.g., noticing predators on the sides while swimming forward or observing stationary telephone poles through the window while traveling by train). An adequate OKR indicates an intact visual pathway, becoming an exceptional tool to uncover vision abnormalities in disease animal models and patients. 

We have developed very simple and accurate methods to measure OKR in zebrafish larvae (between 5 and 21 days old). These methods can also be used to assess visual acuity and contrast sensitivity, and to identify genetic or environmental factors that may alter visual function. 

What inspired you to investigate this? 

Zebrafish are widely used to investigate the biology of vision and blindness as large clutches of embryos are readily obtained, which morphologically develop eyes within 24 hours, and by 5 days post-fertilisation exhibit functional vision, including a robust OKR. 
 
Our laboratory has a lot of experience working with zebrafish to investigate diseases of the eye, drug delivery, and cancer, and there is an increasing need for tests and experimental models to understand and characterize eye diseases.  

However, commonly, OKR analyses in zebrafish only utilize one standard and 100% black and white contrast stripes, which is insufficient to detect subtle impairments in vision.  

Similarly, when we started our project, the only way to test visual acuity (the ability to see objects clearly) and contrast sensitivity (the ability to distinguish between an object and the background behind it) in zebrafish was by using sophisticated set-ups and specialized software for automated or semi-automated OKR research.  

These set-ups require expensive equipment which is not accessible to most research groups.  

As a result, a new method was needed, so we devised a very simple and affordable alternative set-up using a collection of printed black-white or grey-white striped cylinders (printed on regular white cardboard). 

What were the outcomes of your research? 

We made an extensive description of the optokinetic response, visual acuity, and contrast sensitivity in zebrafish, beyond what researchers have done in the field. We found that OKR varies significantly with the age of the fish, time of the day, and the light luminance (the position and intensity of the light source), which is very important from an experimental design point of view.   

In short, our simplified OKR set-up can be used to measure standard responses, visual acuity, and contrast sensitivity as effectively as automated machines whilst being at least 10 times more economical. On top of that, the method allows for a more accurate assessment of visual acuity than that done by currently available software.  

Why is open research important to you and your co-authors? 

Our innovative method is part of the very small but growing discipline of ocular research in zebrafish, and for that reason, the open and public discussion with reviewers can be extremely helpful for the scientific community and for us as researchers to develop future studies.   

Also, we (all the co-authors of this Method Article) fully agree with the European Commission’s line of thought and policies to support and achieve universal open research in the near future. 

What motivated you to publish with Open Research Europe? 

Our research team values Open Research Europe as a public, transparent, and trustworthy publishing platform across research disciplines.  

Publishing on Open Research Europe has been our goal since we started preparing the manuscript, as this project has been financed by Horizon 2020 research and innovation programme under Marie-Sklodowaska-Curie Actions agreements CRYSTAL3 and 3D NEONET.  

The open peer review process has been an incredibly interesting, useful, and recommendable experience. 

What are your next steps? 

We have recently published another article on Open Research Europe using our manual OKR method to investigate the ocular toxicity effects of some common substances in zebrafish eyes.  

Check out our Research Article on Open Research Europe for the fascinating results!