Unilateral optic nerve crush induces bilateral retinal glial cell proliferation

The post‐injury responses of retinal ganglion cells elicit a number of glial reactions which have not been completely understood. The bilateral pattern of non‐neuronal retinal cell proliferation was examined in association with the differential fates of unilaterally injured adult retinal ganglion cells by means of bromodeoxyuridine (BrdU) immunocytochemistry. Lateralization of the glioproliferative events was studied by analysing both the experimental and the uninjured contralateral as well as matched retinas of sham‐operated animals. Control adult rat retina included very few BrdU‐positive cells within the nerve fibre and ganglion cell layers; however, experimental retinas of degenerating groups exhibited statistically significantly higher densities of newborn cells in most layers. Clusters of labelled cells were found in the inner plexiform layer related to OX‐42 staining, indicating their microglial nature. Indeed, double‐labelling experiments, after short‐term unilateral optic nerve crushing, identified proliferating retinal glial cells in vivo. Both types of glia, astroglial and microglial cells, exhibited BrdU‐positive labelling in injured as well as uninjured experimental rat retinas. Moreover, microglial proliferating cells were also identified in explanted retinal pieces after 2 days in culture. Affected and contralateral retinas responded similarly to the unilateral experimental manipulations applied with respect to BrdU labelling. The acute glial responses observed suggest that bilateral glial proliferation might represent a common response related to degeneration events in both retinas, i.e. ipsi‐ and contralateral to the experimental injury.

[1]  Georg W. Kreutzberg,et al.  Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function , 1999, Brain Research Reviews.

[2]  Lieberman Ar.  The Axon Reaction: A Review of the Principal Features of Perikaryal Responses to Axon Injury , 1971 .

[3]  J. García-Verdugo,et al.  Regeneration of a germinal layer in the adult mammalian brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[4]  S. Jander,et al.  The role of microglia and macrophages in the pathophysiology of the CNS , 1999, Progress in Neurobiology.

[5]  S. Thanos,et al.  The concept of microglia in relation to central nervous system disease and regeneration , 1996, Progress in Neurobiology.

[6]  T. Chan‐Ling.  Glial, vascular, and neuronal cytogenesis in whole‐mounted cat retina , 1997, Microscopy research and technique.

[7]  A. Bruce-Keller.  Microglial–neuronal interactions in synaptic damage and recovery , 1999, Journal of neuroscience research.

[8]  A. Dick,et al.  Generation of activated sialoadhesin-positive microglia during retinal degeneration. , 2003, Investigative ophthalmology & visual science.

[9]  M. Kamermans,et al.  Pseudo-immunolabelling with the avidin–biotin–peroxidase complex (ABC) due to the presence of endogenous biotin in retinal Müller cells of goldfish and salamander , 1997, Journal of Neuroscience Methods.

[10]  A. Lieberman.  The axon reaction: a review of the principal features of perikaryal responses to axon injury. , 1971, International review of neurobiology.

[11]  Michael W. Miller,et al.  Use of bromodeoxyuridine-immunohistochemistry to examine the proliferation, migration and time of origin of cells in the central nervous system , 1988, Brain Research.

[12]  Z. Setkowicz,et al.  Contralateral response of macrophages and astrocytes to injury in the cerebral hemisphere of 6-day-old rat following prenatal gamma irradiation , 2004, International Journal of Developmental Neuroscience.

[13]  W. Thomas,et al.  Brain macrophages: on the role of pericytes and perivascular cells , 1999, Brain Research Reviews.

[14]  H. Holländer,et al.  A small population of retinal ganglion cells projecting to the retina of the other eye , 2004, Experimental Brain Research.

[15]  H. Müller,et al.  Experimental strategies to promote axonal regeneration after traumatic central nervous system injury , 1998, Progress in Neurobiology.

[16]  B. Dreher,et al.  Glial reactivity in the retina of adult rats , 1995, Glia.

[17]  P. Richardson,et al.  Regeneration and retrograde degeneration of axons in the rat optic nerve , 1982, Journal of neurocytology.

[18]  I. Ahmad,et al.  Identification of neural progenitors in the adult mammalian eye. , 2000, Biochemical and biophysical research communications.

[19]  M. Schwartz,et al.  Optic nerve disease and injury: Prospects for induction of regeneration , 1996, Progress in Retinal and Eye Research.

[20]  P. Chow,et al.  Bilateral biochemical and biophysical retinal changes after unilateral ocular trauma in the mouse , 1996, Neuroscience Letters.

[21]  H. Aldskogius,et al.  Central neuron–glial and glial–glial interactions following axon injury , 1998, Progress in Neurobiology.

[22]  S. Thanos,et al.  Unilateral injury to the adult rat optic nerve causes multiple cellular responses in the contralateral site. , 1999, Journal of neurobiology.