Unilateral optic nerve crush induces bilateral retinal glial cell proliferation

Abstract

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.

Up‐regulation of crystallins is involved in the neuroprotective effect of wolfberry on survival of retinal ganglion cells in rat ocular hypertension model

“…If we used the protocol like Piri et al by comparing the OH eye with the control eye, our conclusion would also indicate that OH caused down regulation of crystallins in the OH eye. There are increasing lines of evidence that unilateral nerve injury evokes contralateral responses [Bodeutsch et al, 1999;Kleinschnitz et al, 2005;Panagis et al, 2005]. Induction of OH in the right eyes may also cause stress in the contra-lateral left control eyes; and therefore, the use of the contralateral retina as a control in experimental glaucoma study is questionable.…”

“…The average density of RGCs was calculated for the entire retina. Changes in the density of RGCs were expressed as a percentage loss of RGCs by comparing the laser treated right eye and normal control eye [Panagis et al, 2005]:…”

Retinal Metabolic Changes in an Experimental Model of Optic Nerve Transection by Ex Vivo 1H Magnetic Resonance Spectroscopy

“…Gln. * P \ 0.05, *** P \ 0.001 relative to the Con group the right eyes were not used as controls because insulting unilateral optic nerve may affect the morphology and metabolism of the contralateral optic nerve and retina [26].…”

Evidence for Extrathymic Generation of Regulatory T Cells Specific for a Retinal Antigen

“…If recognition of Ag of retinal origin leading to development of T reg involves local collection of Ag and its transfer to peripheral lymphoid tissues for presentation to CD4 T cells, then altering this process could affect the periph- eral development of T reg activity. Extraocular injury (crush) to the optic nerve is well known to induce apoptosis in retinal ganglion cells and lead to retinal micro glial and astroglial activation [16] . In related studies, we have found that a significant number of cells with a dendritic cell phenotype (CD11c+I-A k +) appear in the retina within a few days of an optic nerve crush (unpublished results).…”