Abstract
For years it has been known that unilateral optic nerve lesions induce a bilateral response that causes an inflammatory and microglial response in the contralateral un-injured retinas. Whether this contralateral response involves retinal ganglion cell (RGC) loss is still unknown. We have analyzed the population of RGCs and the expression of several genes in both retinas of pigmented mice after a unilateral axotomy performed close to the optic nerve head (0.5 mm), or the furthest away that the optic nerve can be accessed intraorbitally in mice (2 mm). In both retinas, RGC-specific genes were down-regulated, whereas caspase 3 was up-regulated. In the contralateral retinas, there was a significant loss of 15% of RGCs that did not progress further and that occurred earlier when the axotomy was performed at 2 mm, that is, closer to the contralateral retina. Finally, the systemic treatment with minocycline, a tetracycline antibiotic that selectively inhibits microglial cells, or with meloxicam, a non-steroidal anti-inflammatory drug, rescued RGCs in the contralateral but not in the injured retina. In conclusion, a unilateral optic nerve axotomy triggers a bilateral response that kills RGCs in the un-injured retina, a death that is controlled by anti-inflammatory and anti-microglial treatments. Thus, contralateral retinas should not be used as controls.
Highlights
Optic nerve axotomy is a great model to study in vivo the effect of a localized axonal trauma to the central nervous system (CNS)
In agreement with previous reports [3,6], retinal ganglion cell (RGC) death was first significant at day 3 after the optic nerve crush (ONC) and proceeded quickly up to 14 days, when ~9% of the original population of RGCs survived
We showfor the first time that in pigmented mice the intraorbital distance at which the optic nerve is axotomized does not affect the course of RGC loss in the injured retina, but that it influences the kinetics of RGC loss in the contralateral un-injuredone
Summary
Optic nerve axotomy is a great model to study in vivo the effect of a localized axonal trauma to the central nervous system (CNS). This lesion affects retinal ganglion cells (RGCs) without causing the retrograde death of other retinal neurons, [1] displaced amacrine cells in the ganglion cell layer exhibit some nuclear atrophy [2]. The course of RGC death induced by optic nerve axotomy has been thoroughly studied by our group and others [3,4,5,6,7,8,9,10,11]. During the first 9–14 days, 85% of RGCs are lost. Thereafter, RGCs die more slowly, and by day 90 only 1.5% survive (reviewed in [12])
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