Browsing by Subject "Axonal regeneration"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- PublicationOpen AccessComplementary research models and methods to study axonal regeneration in the vertebrate retinofugal system(Springer, 2018) Bollaerts, Ilse; Veys, Lien; Geeraerts, Emiel; Andries, Lien; De Groef, Lies; Buyens, Tom; Moons, Lieve; Van Hove, Inge; Salinas Navarro, Manuel Ángel; Anatomía Humana y PsicobiologíaDue to the lack of axonal regeneration, age-related deterioration in the central nervous system (CNS) poses a significant burden on the wellbeing of a growing number of elderly. To overcome this regenerative failure and to improve the patient’s life quality, the search for novel regenerative treatment strategies requires valuable (animal) models and techniques. As an extension of the CNS, the retinofugal system, consisting of retinal ganglion cells that send their axons along the optic nerve to the visual brain areas, has importantly contributed to the current knowledge on mechanisms underlying the restricted regenerative capacities and to the development of novel strategies to enhance axonal regeneration. It provides an extensively used research tool, not only in amniote vertebrates including rodents, but also in anamniote vertebrates, such as zebrafish. Indeed, the latter show robust regeneration capacities, thereby providing insights into the factors that contribute to axonal regrowth and proper guidance, complementing studies in mammals. This review provides an integrative and critical overview of the classical and state-of-the-art models and methods that have been employed in the retinofugal system to advance our knowledge on the signaling pathways underlying the restricted versus robust axonal regeneration in rodents and zebrafish, respectively. In vitro, ex vivo and in vivo models and techniques to improve the visualization and analysis of regenerating axons are summarized. As such, the retinofugal system is presented as a valuable model to further facilitate research on axonal regeneration and to open novel therapeutic avenues for CNS pathologies.
- PublicationOpen AccessMMP2 Modulates Inflammatory Response during Axonal Regeneration in the Murine Visual System(MDPI, 2021-07-02) Andries, Lien; Masin, Luca; Salinas Navarro, Manuel Ángel; Zaunz, Samantha; Claes, Marie; Bergmans, Steven; Brouwers, Véronique; Lefevere, Evy; Verfaillie, Catherine; Movahedi, Kiavash; De Groef, Lies ; Moons, Lieve; Anatomía Humana y Psicobiología; Facultades de la UMU::Facultad de MedicinaNeuroinflammation has been put forward as a mechanism triggering axonal regrowth in the mammalian central nervous system (CNS), yet little is known about the underlying cellular and molecular players connecting these two processes. In this study, we provide evidence that MMP2 is an essential factor linking inflammation to axonal regeneration by using an in vivo mouse model of inflammation-induced axonal regeneration in the optic nerve. We show that infiltrating myeloid cells abundantly express MMP2 and that MMP2 deficiency results in reduced long-distance axonal regeneration. However, this phenotype can be rescued by restoring MMP2 expression in myeloid cells via a heterologous bone marrow transplantation. Furthermore, while MMP2 deficiency does not affect the number of infiltrating myeloid cells, it does determine the coordinated expression of pro- and anti-inflammatory molecules. Altogether, in addition to its role in axonal regeneration via resolution of the glial scar, here, we reveal a new mechanism via which MMP2 facilitates axonal regeneration, namely orchestrating the expression of pro- and anti-inflammatory molecules by infiltrating innate immune cells.
- PublicationOpen AccessWnt5a regulates the expression of developmental genes in the adult retina following optic nerve crush injury(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Albano Gabrielle A.; Parrales Paola E.; Hackam Abigail S.; Biología Celular e HistologíaCanonical and non-canonical Wnt signaling pathways are well-characterized regulators of retinal development. Wnt signaling also promotes neuro-protection and regeneration in adult tissues, including retinal ganglion cell (RGC) survival and axonal regrowth after optic nerve injury. However, it is unknown whether Wnt-dependent neuroprotection after injury in the adult CNS is associated with altered expression of developmental genes. Müller glia are a prominent radial glia type in the retina that play critical roles in retinal neuron protection, RGC neurite growth, and axon regeneration by acting through Wnt and other signaling pathways. We recently used mass spectrometry to characterize proteins secreted from Müller glia in response to Wnt signaling. In this study, we investigated whether the Wnt-induced Müller glia secretome includes proteins involved in development and whether their corresponding genes are regulated by Wnt5a during axonal regeneration in a mouse model of optic nerve crush (ONC) injury. Adult mice received intravitreal injections of Wnt5a or saline at the time of ONC injury, and then retina tissue was collected at early time points post-injury. The expression of candidate Wnt-regulated developmental genes and related proteins were characterized by qPCR and immunohistochemistry. Our findings revealed that Wnt5a downregulated the expression of specific developmental genes, including cilia-related genes Nphp4, INTU, and Jade1, as well as transcriptional regulators Pax6 and Tsc1, with time-dependent changes observed during axonal regrowth. Several of these genes were localized to RGCs and inner nuclear layer cells, suggesting direct effects in RGCs and contributions from Müller glia. These results demonstrate that specific developmental gene pathways are suppressed by Wnt5a in association with RGC survival and axon regrowth following injury. Therefore, this study adds to our knowledge of potential mechanisms of Wnt-mediated optic nerve regeneration and identifies new categories of putative regeneration-regulating genes for further study