Visualising Vision in Zebrafish

By Dr. Elisabeth Kugler and Dr. Ryan MacDonald

The importance of vision research

The eye is the sensory organ that relays visual information from the outside world to our brain via the light-sensitive retina. The human retina is only about 250 micrometers in thickness, which is about a third of a credit card or an eighth of a spaghetti noodle. Yet, it is formed by 9 cell types (5 neurons, 3 glia, and blood vessels), with over 60 subtypes existing for neurons alone, highlighting the intricacy and complexity of the retina.

In our body, cells can generally be constantly renewed (like your skin for example), but this is not the case in the retina, where cells that are lost will be lost forever. So the retinal cells that we are born with are the ones we die with. As such, our whole life is a very long time for cells to survive and work perfectly without interruption. Sometimes cells do break down during our lifetime, like when we age or in degenerative disease, which, in the worst case, can lead to vision loss and blindness. Therefore, there is a clear need to learn how the cells in the retina fit together in the healthy eye and what happens when they become ill. To do so, researchers often go back to the very start, namely developmental biology, which is trying to understand how cells and organs form at the very start, informing our knowledge on how these cells function, become ill, and potentially if these mechanisms can be manipulated to find a potential cure.

To study how the retina develops, we need to follow tissue development, growth, and function over time. However, as humans develop inside their mother and the retina is placed at the back of our eye, we cannot simply observe to study those cells. To get around these obstacles we use a model organism where the embryos are external to the mother and light easily passes through them, the answer is a zebrafish. Zebrafish? Yes, zebrafish. The ones you can buy in the pet shop! “There is no light without darkness” Mark Frost

How zebrafish can help us understand vision

Zebrafish are more similar to humans than one might think. Zebrafish and humans share about 70% of genes, allowing us to study the role of these genes in zebrafish and translate that knowledge to humans. Also, zebrafish develop rapidly outside the mother and grow from a single-cell to a free-swimming larva, complete with organ systems, in about three days. This enables us to investigate fundamental developmental mechanisms in very short time frames if compared to humans.

One of the most fascinating characteristics is that zebrafish larvae are almost transparent, so we can look directly inside their brain and eye to study their development. Even so, zebrafish larvae are smaller than the tip of a match stick and the cells in the retina are smaller than 10 micrometers, which is about the size of a single red blood cell. Thus, to study how the cells in the retina develop and function, microscopy is needed. To visualize the tissues and biological events we are interested in, we use fluorescent proteins that visualize all kinds of different tissues with different colours, such as blood cells in red, nerve cells in green, or muscles in blue.

How science impacts art

The transformation of science into images allows us to share our vision research very naturally as imagery and visual art. Elisabeth always had a passion for both science and art. She integrates her artistic knowledge into our science communication when displaying actual microscopy data, but applies artistic freedom on aspects such as colour, composition, or perspective.

This combination of scientific and artistic knowledge allows her to highlight selected image features, increase the visual impact, and facilitate communication across ages, backgrounds, and interests. Importantly, one does not necessarily need to understand the image content but assess whether they like it or not based on the evoked emotional response. For us, this means that we can share our fascination for research and science using visuals that hopefully inspire others.

When studying vision, we do this in living tissues, and despite common belief, cells, tissues, and organs are not stationary, but in constant movement and change. When considering this as a starting point, this drastically changes our imagery and emanates in extraordinary colour combinations, angles, and video sequences. Similarly, cells are not alone, but interact with others via an incredible spatial organisation, allowing them to interact with other cells and cell types.

However, simply looking at the zebrafish larvae, one does not directly see something as the fluorescent proteins need energy. This energy is supplied by a highly focused beam of light, namely lasers of nature specific to the fluorescent protein that we are interested in. Once the fluorescent proteins have enough energy, they start to emit this energy back as light. This emitted light is what can then be captured using a camera, and transforms science into images.

Again, these individual interactions are very dynamic, and using state-of-the-art microscopy we can begin to unravel these dynamics in 4Dimensions (D)+ (3D, time, different wavelengths, etc). One of Elisabeth’s favourite science moments is still the first time that she saw a green beating heart in a living zebrafish through a microscope. This is over a decade ago, yet it encompasses her fascination for science, art, and dynamics as well as light, microscopy, and vision all in one memory. Ryan can’t get over how beautiful and intricate the retina is. He’s spent his entire scientific career enthralled by how cells somehow fit together and make connections in the embryo such that a baby can see at birth!

Using a zebrafish embryo allows us to watch the intricate dance of cells trying to find their partners and fit into a larger puzzle. It’s as if we have a window to the party. Visualising these events and understanding the secrets of eye development is what excites Ryan the most and keeps him coming back for more.

How art impacts science...

And vice versa, art influences science. In our case, this is less about how we conduct science rather than how we represent our data and communicate them. This is best exemplified by studying threedimensional data in two dimensions using a depthcoding-based approach.

This means that structures are assigned colours based on the anatomical location. Using this initially for pure science communication, the lab and others use this technique now for scientific communication and publications.

In her free time, Elisabeth likes to draw and paint. Here, her scientific work influences her art often more indirectly and subtly, e.g. in terms of colourgradients or shapes. For her, (science-)art has the most significant impact on her scientific work by improving her overall communication skills; and this is mainly due to two reasons.

Firstly, while science is often communicated within a highly specialized field and scientific niche, art is often communicated to and shared with a wider community. Thus, communicating art requires a distinct communication skill-set from science. Secondly, engaging with people other than researchers from one’s field means being exposed to additional ways of thinking and questions. Additionally, engaging with art exposes one to myriads of things beyond their research, creating new opportunities and networks.

The appreciation for the fact that arts and sciences are not separate but inspire each other is not a new concept, but something that has repeated itself in history. The most famous examples are people such as Leonardo da Vinci or Santiago Ramón y Cajal. Back in those days, there were no cameras or microscopes to visualize and eternalize scientific findings and observations, but everything needed to be documented by highly detailed drawings and descriptions. These documents were of such high quality that some of those are exhibited nowadays as artwork in art galleries around the world.

So we believe that while the concept of scienceart is clearly not new, the new ways to visualize and manipulate research data opens up new avenues to share our science with others.

Together, it becomes clear that science and art are not separate, but interwoven and when combined intelligently and efficiently they can support each other, building a synergy that makes each field stronger than they would be on their own.

About the team Find out more

Elisabeth Kugler and Ryan MacDonald are scientists at the University College London, studying how cells form functional complexes during eye development. Their work heavily relies on microscopy images to examine cells on a subcellular level. Images from both their work have been featured on several covers. Over the last few years, Elisabeth has merged her interest in drawing and painting with her scientific microscopy images, creating digital media science art to share and advocate science with others. Elisabeth Kugler Website: www.ElisabethKugler.com Twitter: @KuglerElisabeth

MacDonald Lab Website: zebrafishucl.org/macdonald-lab Twitter: @MacDonald_Lab