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Review
. 2024 Sep 4:11:1393057.
doi: 10.3389/fmed.2024.1393057. eCollection 2024.

The mechanics of the retina: Müller glia role on retinal extracellular matrix and modelling

Affiliations
Review

The mechanics of the retina: Müller glia role on retinal extracellular matrix and modelling

Laura Prieto-López et al. Front Med (Lausanne). .

Abstract

The retina is a highly heterogeneous tissue, both cell-wise but also regarding its extracellular matrix (ECM). The stiffness of the ECM is pivotal in retinal development and maturation and has also been associated with the onset and/or progression of numerous retinal pathologies, such as glaucoma, proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), epiretinal membrane (ERM) formation or uveitis. Nonetheless, much remains unknown about the biomechanical milieu of the retina, and specifically the role that Müller glia play as principal mechanosensors and major producers of ECM constituents. So far, new approaches need to be developed to further the knowledge in the field of retinal mechanobiology for ECM-target applications to arise. In this review, we focus on the involvement of Müller glia in shaping and altering the retinal ECM under both physiological and pathological conditions and look into various biomaterial options to more accurately replicate the impact of matrix stiffness in vitro.

Keywords: Müller glia; extracellular matrix; hydrogels; retina; stiffness.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Cell-matrix interactions. There is a two-way communication between the ECM and Müller glia; ECM influences the celular outcome while those same cells organize the ECM. Created with BioRender.com.
Figure 2
Figure 2
ECM distribution in the retina. Differential distribution of ECM components among the retinal layers; from outermost to innermost: retinal pigment epithelium (RPE), photoreceptor segment (PRS), outer limiting membrane (OLM), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), ganglion cell layer (GCL), nerve fiber layer (NFL), optic nerve (ON). Müller glia (blue). Created with BioRender.com.
Figure 3
Figure 3
Schematic representation of the feed-forward loop generated by ECM stiffness in retinal fibrosis. Matrix stiffness promotes YAP nucleus translocation and activation, thus increasing cell proliferation and collagen deposition, increasing substrate stiffness in a feed-forward loop. Created with BioRender.com.
Figure 4
Figure 4
Müller glia-driven alterations in retinal ECM stiffness involvement in retinal diseases. Schematic representation of different retinal pathologies in which ECM deposition and increased stiffness via activated Müller glia is involved and known mechanisms. Created with BioRender.com.

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