Image of neuron connections in the retina

We funded Dr Ryan MacDonald and Dr Elisabeth Kugler to create GliaMorph, an image analysis toolkit for studying connections between glial cells and neurons, aiding research on retinal diseases.

We supported Dr Ryan MacDonald and Dr Elisabeth Kugler with a Springboard award to develop GliaMorph computational toolkit. 

This image analysis pipeline will help researchers and clinicians study how glial cells connect with neurons. This in turn will help better understand the role that the glial cells play in many retinal diseases.

Quantifying cell morphology

It is an ongoing challenge to quantify cell morphology accurately and reproducibly. Computational analysis is paramount to model cell function and connectivity in the context of complex living tissues.

Glial cells provide a myriad of functions in the central nervous system (CNS) and retina. 

They are precisely shaped to contact both neurons and their synapses, and blood vessel to altogether form retinal neurovascular unit (NVU).

Retinal neurovascular unit

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The retinal NVU is made up of neurons, blood vessels (visualised as magenta cells on the image above) and dedicated support cells called glia (blue cells). These different types of cells come together during eye development and go onto support the retina throughout life. This system is known to break down in disease, such as diabetic retinopathy. Without it, the retina cannot function properly and starts to degenerate, leading to vision loss.

Glial cells shape is pivotal to healthy CNS tissue and it is altered in numerous neurodegenerative conditions, including epilepsy and diabetic retinopathy.

Deeper insight with GliaMorph

GliaMorph is a modular image analysis toolkit developed for image pre-processing, glial segmentation, and cell quantification. 

Drs MacDonald and Kugler used and validated the GliaMorph toolkit by studying Muller glial (MG) cells, which are the main type found in retina. 

The GliaMorph toolkit enabled deeper understanding of MG morphology in the developing and diseased retina.

Our data quantitatively describe how glia cells develop and what meaningful parameters can be used to describe this.

Dr Elisabeth Kugler

GliaMorph was applied in a wide range of experiments and allowed Dr MacDonald’s research group to gather new data and insights to:

  • describe structural changes occurring in the developing retina
  • quantify over 20 morphological characteristics of glial development
  • examine glial cells function and inflammatory markers in glaucoma mouse disease model

GliaMorph complements the state-of-the-art molecular biology and microscopy techniques that the team uses to study and understand the formation of retinal NVU. 

Notable outcomes

The results highlight that it is a dynamic process. Glial cells react readily to environmental cues and change the shape of their neuronal projections in response to neuronal activity and upon contact with blood vessels to form specialised connections.

These computational tools are pivotal to future studies of extracellular matrix biology in the retina, glial development and disease.

Dr Ryan MacDonald

GliaMorph protocols and applications were recently published in open access journals Current Protocols, January 2023 and made the cover article for the prestigious journal Development, February 2023.

This will help fulfil the potential of the newly developed GliaMorph data analysis toolkit to be widely applicable and transferable to other projects.

Focus on early career researcher

Dr Elisabeth Kugler

During her post at Dr MacDonald’s lab, Dr Kugler:

  • produced one data analysis toolkit, 5 datasets, freely shared all computational codes and one YouTube channel
  • contributed to 2 publications, one highly cited review and presented at multiple scientific conferences
  • won the prestigious Rank Prize Seeing Science photography competition in the Optoelectronics category 2020
  • contributed to dissemination of scientific knowledge by reviewing scientific manuscripts and engaging with wider audience through social media
  • completed 15 continuous professional development courses and gained associate fellowship accreditation from the Higher Education Academy

Dr Kugler has now started the Zeeks company that delivers bespoke data analysis approaches and turns scientific images into art.