Research

The overarching research aim of my laboratory is to understand how a healthy eye is built and maintained throughout life. More specifically, we are interested in how glial cells, the major support cells in the nervous system, are patterned and shaped during development to support neurons. We are also interested in what happens when the intricate glia-neuronal relationship breaks down due to increasing age or disease.

The retina is the light sensitive part of the eye that allows you to see. We use the zebrafish retina as a model as it contains the same neuron types and glial cells as the human eye. The zebrafish embryo is an incredible system to study development – it is transparent, we can label each cell with specific fluorescent markers and use time-lapse confocal microscopy to watch eye development happen in real time in a living fish! In addition to imaging we use CRISPR/Cas9 mutagenesis, RNA-sequencing and molecular biology to uncover and explore fundamental mechanisms of glial biology.

We are now interested in determining the cellular and molecular mechanisms regulating glial morphogenesis, with a particular focus on the consequences of disrupted glial contacts on neuronal function.

Click the buttons below to learn more about our different research topics. Visit our Resources page to access tools, protocols and view our antibody and transgenic line data.

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Current members

MacDonald Lab News 

Our Covers

SELECTED Publications (Full list)

2024

Bergmans S§, Noel NCL§, Masin L, Harding E, Krzywanska AM, Rajagopal A, Hu CK, Arckens L, Ruzycki PA*, MacDonald RB*, Clark BS*, Moons L*. 2024. Age-related dysregulation of the retinal transcriptome in the African turquoise killifish. Submitted. *Co-corresponding authors. bioRxiv: http://biorxiv.org/content/early/2024/02/23/2024.02.21.581372

Kothurkar A§, Patient GS§, Noel NCL, Chu CJ*, MacDonald RB*. Iterative Bleaching Extends Multiplexity (IBEX) Imaging facilitates simultaneous identification of all cell types in the vertebrate retina. *Corresponding author. bioRxiv: https://www.biorxiv.org/content/10.1101/2024.02.28.582563v1?ct=

Farger E, Keatinge M, Pearce O, Piepponen P, Paula P, van Eden F, MacDonald RB, Bandmann O. A Zebrafish Model of α-Amino-β-Carboxymuconate-εSemialdehyde Decarboxylase Deficiency. Submitted.

2023

Jaroszynska N, Salzinger A, Tsarouchas T, Becker CG, Becker T, Lyons D, MacDonald RB*, Keatinge M*. C9ORF72 deficiency results in degeneration of the zebrafish retina in vivo. Submitted. bioRxiv: https://www.biorxiv.org/content/10.1101/2023.10.19.563041v1?ct=

Uttley K, Papanastasiou AS, Lahne M, Brisbane J, MacDonald RB, Bickmore WA, Bhatia S. 2023. Unique functions of two overlapping PAX6 retinal enhancers. Life Science Alliance. 6(11):e20230212. https://doi.org/10.26508/lsa.202302126 *Co- corresponding author.

Keatinge M§, Gegg ME§, Watson L, Mortiboys H, Bui H, Lefeber DJ, van Rens A, MacDonald RB*, Bandmann O*. 2023. Unexpected phenotypic and molecular changes of combined glucocerebrosidase and acid sphingomyelinase deficiency. Disease models and mechanisms. https://journals.biologists.com/dmm/article/16/6/dmm049954/308903/ *Co- corresponding author.

Kugler E, Bravo I, Durmishi X, Marcotti S, Beqiri S, Carrington A, Stramer BM, Mattar P, MacDonald RB. 2023. GliaMorph: A modular image analysis toolkit to quantify Müller glial cell morphology. Development: 150(3):dev201008. https://doi.org/10.1242/dev.201008

Kugler E*, Breitenbach E-M, MacDonald RB*. 2023. Glia cell morphology analysis using the Fiji GliaMorph toolkit. Current Protocols. *Co- corresponding author. https://doi.org/10.1002/cpz1.654.

2022

Martins RR, Zamzam M, Moosajee M, Thummel R, Henriques CM*, MacDonald RB*. 2022. Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina. Ageing Cell. 21:e13597. *Co- corresponding author. https://doi.org/10.1111/acel.13597

Larbalestier H, Keatinge M, Watson L, White E, Gowda S, Wei W, Koler K, Semenova SA, Rimmer N, Sweeney ST, Mazzolini J, Sieger D, McDearmid J, Panula P, MacDonald RB*, Bandmann O*. 2022. GCH1 Deficiency Activates Brain Innate Immune Response and Impairs Tyrosine Hydroxylase Homeostasis. J Neurosci. 42(4):702-716. *Co-corresponding authors. https://doi.org/10.1523/JNEUROSCI.0653-21.2021

Schlaeppi A, Adams W, Haase R, Huisken J, MacDonald RB, Eliceiri K and Kugler E. 2022. Meeting in the middle: towards successful multidisciplinary bioimage analysis collaborations. Frontiers in Bioinformatics. https://doi.org/10.3389/fbinf.2022.889755

Jurisch-Yaksi N, Kugler EC, MacDonald RB, Mosimann C, and Yaksi E. 2022. Microscopy techniques in zebrafish. RMS inFocus. https://www.rms.org.uk/resource/elisabeth-kugler-pdf.html

2021

Kugler EC, Greenwood, J and MacDonald RB. 2021. The “Neuro-glial-vascular” unit: The role of glia in retina and brain neurovascular unit formation. Review Article. Front. Cell. Dev. Biology. https://doi.org/10.3389/fcell.2021.732820

Turan F, Yilmaz O, Schünemann L, Kleinert H, Ahmadi S, Duman T, MacDonald RB, Liu C, Winter D, Odermatt B. 2021. Effect of modulating glutamate signaling on myelinating oligodendrocytes and their development a study in the zebrafish model. Journal of Neuroscience Research. https://doi.org/10.1002/jnr.24940

2019

Chhabria K, Vouros A, Gray C, MacDonald RB, Wilkinson RW, Plant K, Vasilaki E, Howarth C, Chico TJA. 2019. Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish. Disease Models and Mechanisms. §Cover Article. https://doi.org/10.1242/dmm.039867

Kugler EC, van Lessen M, Daetwyler S, Chhabria K, Savage AM, Silva V, Plant K, MacDonald RB, Huisken J, Wilkinson RN, Schulte-Merker S, Armitage P, Chico TJA. 2019. Cerebrovascular endothelial cells form transient Notch-dependent cystic structures in zebrafish. EMBO Rep. 20:e47047. §Cover Article. https://doi.org/10.15252/embr.201847047

Charlton-Perkins M, Almeida AA, MacDonald RB* and Harris WA*. 2019. Genetic control of cellular morphogenesis in Müller glia. Glia. .*Co-senior corresponding author. § Cover Article. https://doi.org/10.1002/glia.23615

Savage AM, Kurusamy S, Chen Y, Jiang Z, Chhabria K, Kim HR, Wilson HL, MacDonald RB, van Eeden FJM, Armesilla AL, Chico TJA, Wilkinson RN. 2019. tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis. Nature Comms. 10:732. https://doi.org/10.1038/s41467-019-08590-7

Martins, RR, Ellis. PS, MacDonald RB, Richardson RJ, Henriques, CM. 2019. Resident immunity in tissue repair and maintenance: the zebrafish model coming of age. Front. Cell Dev. Biol. https://doi.org/10.3389/fcell.2019.00012

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 Our work is generously supported by the following funders: