Abstract
In response to injury, the adult mammalian retina shows signs of structural remodeling, possibly in an attempt to preserve or regain some of its functional neural connections. In order to study the mechanisms involved in injury-induced plasticity, we have studied changes in growth associated protein 43 (GAP-43) after retinal ischemia/reperfusion in the rat. GAP-43 is a marker for neuronal remodeling and is involved in synapse formation. Ischemic injury of the rat retina was induced by 60 min of ischemia followed by reperfusion times varying from 2 h up to 4 weeks. GAP-43 mRNA levels were significantly increased between 12 h and 72 h reperfusion with a peak around 24 h. GAP-43 specific antibodies showed that the total amount of GAP-43 labeling in the inner plexiform layer was diminished after 12 h of reperfusion by approximately 35% and remained at this level up to 1 week postischemia despite the reduction in thickness of this layer during this period resulting from the ischemia-induced cell loss. At 2 and 4 weeks reperfusion, the amount of labeling was reduced by 70%, simultaneously with a decrease of GAP-43 transcript level. Between 72 h up to 2 weeks postischemia, the induction of intense GAP-43 labeling was observed in NeuN- and β-tubulin-positive ganglion cell somata and in horizontally and vertically oriented processes in the inner plexiform layer. Ischemia also induced GAP-43 expression in some GFAP-positive Müller cells. Double-labeling showed that in controls and after ischemia GAP-43 was expressed by some amacrine cells of the glycinergic (glycine transporter 1), calretinin-positive, and dopaminergic (tyrosine hydroxylase) subpopulations. No increase of GAP-43 expression levels was found in these amacrine cells. The results demonstrate that ganglion cells show an elevated expression of GAP-43 after ischemia-inflicted damage. These findings suggest a temporal window during which ganglion cells may remodel their neuronal network in the damaged retina.
Original language | English |
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Pages (from-to) | 858-867 |
Number of pages | 10 |
Journal | Experimental eye research |
Volume | 84 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2007 |
Keywords
- GAP-43
- amacrine cells
- glaucoma
- immunocytochemistry
- ischemia/reperfusion
- neurodegeneration
- neuroregeneration
- plasticity
- quantitative PCR
- retina
- retinal ganglion cells