Abstract

Astrocytes are glial cells that support and protect neurons in the central nervous systems including the retina. Retinal ganglion cells (RGCs) are in contact with the astrocytes and our earlier findings showed the reduction of the number of cells in the ganglion cell layer in adult progranulin deficient mice. In the present study, we focused on the time of activation of the astrocytes and the alterations in the number of RGCs in the retina and optic nerve in progranulin deficient mice. Our findings showed that the number of Brn3a-positive cells was reduced and the expression of glial fibrillary acidic protein (GFAP) was increased in progranulin deficient mice. The progranulin deficient mice had a high expression of GFAP on postnatal day 9 (P9) but not on postnatal day 1. These mice also had a decrease in the number of the Brn3a-positive cells on P9. Taken together, these findings indicate that the absence of progranulin can affect the survival of RGCs subsequent the activation of astrocytes during retinal development.

Highlights

  • Astrocytes are present in the retinal nerve fiber layer (RNFL) and they secrete different types of growth factors and cytokines especially when the retina is injured

  • glial fibrillary acidic protein (GFAP) is a marker of activated astrocytes[18], and a high expression of GFAP showed that the astrocytes were activated in the Grn−/− retina

  • An expression of progranulin was observed around S100β-positive (S100β+) astrocytes and it was co-localized with Iba-1+ microglia (Fig. 1G,H)

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Summary

Introduction

Astrocytes are present in the retinal nerve fiber layer (RNFL) and they secrete different types of growth factors and cytokines especially when the retina is injured. The retinal ganglion cells (RGCs) are located in the ganglion cell layer (GCL) among the astrocytes, and they send their axons toward the optic nerve and to the lateral geniculate nucleus and superior colliculus[3]. APCs in the retina guide the axons toward the optic nerve during embryonic development[2], and they are required for the normal development of the synapses of the RGCs6, 7. Progranulin has been shown to promote neuronal survival and the regulation of inflammation in the brain, retina, and spinal cord[12,13,14,15,16]. We have shown that the retinas of adult progranulin-deficient mice, Grn−/− mice were not normal[17]. The purpose of this study was to determine when the alterations of the RGC and other retinal structures occur in Grn−/− mice

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