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SORLA Expression in Synaptic Plexiform Layers of Mouse Retina

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Abstract

Sorting protein–related receptor containing LDLR class A repeats (SORLA; also known as LR11) exerts intraneuronal trafficking functions in the central nervous system. Recently, involvement of SORLA in retinogenesis was proposed, but no studies have examined yet in detail the expression pattern of this sorting receptor in the retina. Here, we provide a spatio-temporal characterization of SORL1 mRNA and its translational product SORLA in the postnatal mouse retina. Using stereological analysis, we confirmed previous studies showing that receptor depletion in knockout mice significantly reduces the number of cells in the inner nuclear layer (INL), suggesting that functional SORLA expression is essential for the development of this retinal strata. qPCR and Western blot analyses showed that SORL1/SORLA expression peaks at postnatal day 15, just after eye opening. Interestingly, we found that transcripts are somatically located in several neuronal populations residing in the INL and the ganglion cell layer, whereas SORLA protein is also present in the synaptic plexiform layers. In line with receptor expression in dendritic terminals, we found delayed stratification of the inner plexiform layer in knockout mice, indicating an involvement of SORLA in neuronal connectivity. Altogether, these data suggest a novel role of SORLA in synaptogenesis. Receptor dysfunctions may be implicated in morphological and functional impairments of retinal inner layer formation associated with eye disorders.

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Acknowledgements

We are grateful for expert technical assistance from Sandra Bonnesen and Helene Andersen.

Funding

This work is supported by grants from the Novo Nordisk Foundation, the Augustinus Foundation, the Hartmann Foundation, the A. P. Møller Foundation, the Henrik Henriksen Foundation and the Danish Council for Independent Research. Centre for Stochastic Geometry and Advanced Bioimaging is supported by Villum Foundation.

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Authors and Affiliations

  1. Danish Research Institute of Translational Neuroscience (DANDRITE) Nordic-EMBL Partnership, Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, DK-8000, Aarhus C, Denmark

    Giulia Monti, Marianne L. Jensen, Arnela Mehmedbasic, Pernille Barkholt, Egija Zole, Christian B. Vægter & Olav M. Andersen

  2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Margarita Melnikova Jørgensen & Ida E. Holm

  3. Department of Pathology, Randers Regional Hospital, Randers, Denmark

    Margarita Melnikova Jørgensen & Ida E. Holm

  4. Department of Ophthalmology, Aalborg University Hospital, Hobrovej 18-22, DK-9000, Aalborg, Denmark

    Henrik Vorum

  5. Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark

    Jens R. Nyengaard

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  1. Giulia Monti
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Contributions

GM and OA wrote the manuscript. OA coordinated the study. qPCR and in situ studies were performed by EZ and GM. Protein characterization and histological studies in retina samples were carried out by MJ, IH, MK and AM. PB and JN contributed to the stereological analyses. CV, HV and JN provided expert advices, assisting with data interpretation. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Olav M. Andersen.

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All procedures involving animals were conducted in full compliance with the Danish and European regulations.

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Highlights

• SORL1/SORLA is expressed during postnatal mouse retinogenesis.

• SORL1 transcripts are mainly localized somatically in ganglion cells and in the inner nuclear layer.

• Localization in the inner and outer plexiform layers was observed for SORLA receptor.

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Monti, G., Jensen, M.L., Mehmedbasic, A. et al. SORLA Expression in Synaptic Plexiform Layers of Mouse Retina. Mol Neurobiol 57, 3106–3117 (2020). https://doi.org/10.1007/s12035-020-01946-x

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