LPS-stimulated microglial cells promote ganglion cell death in organotypic cultures of quail embryo retina
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Sierra Martín, Ana; Navascues Martínez, Julio; Neubrand, Veronika Elisabeth; Sepúlveda Justo, María Del Rosario; Martín Oliva, Francisco David; Cuadros Ojeda, Miguel Ángel; Marín Teva, José LuisEditorial
Frontiers
Materia
Microglia Retina Quails LPS-stimulation iNOS Nitric oxide Ganglion cell death Organotypic cultures
Date
2023-03-15Referencia bibliográfica
Sierra-Martín A, Navascués J, Neubrand VE, Sepúlveda MR, Martín-Oliva D, Cuadros MA and Marín-Teva JL (2023) LPS-stimulated microglial cells promote ganglion cell death in organotypic cultures of quail embryo retina. Front. Cell. Neurosci. 17:1120400. doi: 10.3389/fncel.2023.1120400
Sponsorship
Ministerio de Economía y Competitividad, Spain (BFU2010-19981); Junta de Andalucía, Spain (P07-CVI-03008)Abstract
During development microglia colonize the central nervous system (CNS) and
play an important role in programmed cell death, not only because of their ability
to remove dead cells by phagocytosis, but also because they can promote the
death of neuronal and glial cells. To study this process, we used as experimental
systems the developing in situ quail embryo retina and organotypic cultures of
quail embryo retina explants (QEREs). In both systems, immature microglia show
an upregulation of certain inflammatory markers, e.g., inducible NO synthase
(iNOS), and nitric oxide (NO) under basal conditions, which can be further
enhanced with LPS-treatment. Hence, we investigated in the present study the
role of microglia in promoting ganglion cell death during retinal development
in QEREs. Results showed that LPS-stimulation of microglia in QEREs increases
(i) the percentage of retinal cells with externalized phosphatidylserine, (ii) the
frequency of phagocytic contacts between microglial and caspase-3-positive
ganglion cells, (iii) cell death in the ganglion cell layer, and (iv) microglial
production of reactive oxygen/nitrogen species, such as NO. Furthermore, iNOS
inhibition by L-NMMA decreases cell death of ganglion cells and increases the
number of ganglion cells in LPS-treated QEREs. These data demonstrate that
LPS-stimulated microglia induce ganglion cell death in cultured QEREs by a NOdependent
mechanism. The fact that phagocytic contacts between microglial
and caspase-3-positive ganglion cells increase suggests that this cell death might
be mediated by microglial engulfment, although a phagocytosis-independent
mechanism cannot be excluded.