Abstract

We have recently described a novel type of glial cell that is scattered across the inner layers of the avian retina [1]. These cells are stimulated by insulin-like growth factor 1 (IGF1) to proliferate, migrate distally into the retina, and up-regulate the nestin-related intermediate filament transitin. These changes in glial activity correspond with increased susceptibility of neurons to excitotoxic damage. This novel cell-type has been termed the Non-astrocytic Inner Retinal Glia-like (NIRG) cells. The purpose of the study was to investigate whether the retinas of non-avian species contain cells that resemble NIRG cells. We assayed for NIRG cells by probing for the expression of Sox2, Sox9, Nkx2.2, vimentin and nestin. NIRG cells were distinguished from astrocytes by a lack of expression for Glial Fibrilliary Acidic Protein (GFAP). We examined the retinas of adult mice, guinea pigs, dogs and monkeys (Macaca fasicularis). In the mouse retina and optic nerve head, we identified numerous astrocytes that expressed GFAP, S100β, Sox2 and Sox9; however, we found no evidence for NIRG-like cells that were positive for Nkx2.2, nestin, and negative for GFAP. In the guinea pig retina, we did not find astrocytes or NIRG cells in the retina, whereas we identified astrocytes in the optic nerve. In the eyes of dogs and monkeys, we found astrocytes and NIRG-like cells scattered across inner layers of the retina and within the optic nerve. We conclude that NIRG-like cells are present in the retinas of canines and non-human primates, whereas the retinas of mice and guinea pigs do not contain NIRG cells.

Highlights

  • The retinas of vertebrates contain many different types of glial cells

  • The increased cell death was prominent within areas of retinal detachment which were coincident with a stark loss of Muller glia and an accumulation of Non-astrocytic Inner Retinal Glia-like (NIRG) cells. These findings indicate that NIRG cells are a novel type of retinal cell that is sensitive to insulin-like growth factor 1 (IGF1) and whose activity impacts the survival of retinal neurons and Muller glia

  • In the retinas of species examined in these studies, astrocytes were identified based on expression of Glial Fibrilliary Acidic Protein (GFAP) and other markers known to be expressed by mature retinal glia including Sox2, Sox9 and S100b [1,9,10,11,12,13,14]

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Summary

Introduction

The retinas of vertebrates contain many different types of glial cells. The primary activities of these glia include retinal homeostasis and support of neuronal function. Retinal glia include Muller glia, derived from retinal stem cells, and microglia, derived from hematopoietic stem cells. With some variations between species, retinal glia can include astrocytes and oligodendrocytes. The avascular retinas of chickens, guinea pigs and rabbits contain oligodendrocytes that myelinate the axons of ganglion cells in the nerve fiber layer (NFL) [2,3,4]. Vascular retinas contain significant numbers of astrocytes that are closely associated with the blood vessels [5,6,7], avascular retinas contain few, if any, astrocytes [1,8]

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