Growth-associated protein 43 is up-regulated in the ganglion cells of the ischemic rat retina

Abstract

We investigated the expression and cellular localization of growth-associated protein (GAP)-43 in the rat retina following ischemia induced by transiently increased intraocular pressure. In the normal retina, GAP-43 immunoreactivity was restricted to profiles in the inner plexiform layer. Following ischemia and reperfusion, immunoreactivity appeared in ganglion cells. The cell density of labeled ganglion cells peaked three days post-lesion and then decreased at seven days. Quantitative evaluation by immunoblotting confirmed that GAP-43 expression increased at three days (to 190% of control levels) and then slightly decreased at seven days. Our findings suggest that some ganglion cells have the potential to regenerate through the up-regulation of GAP-43 in the ischemic rat retina.

Protective effects of triamcinolone acetonide upon the upregulation and phosphorylation of GAP 43 in an animal model of retinopathy of prematurity

“…1994), this developmentally regulated protein can be re‐expressed or increased in various types of damage such as axon injury and ischaemia (Doster et al. 1991; Ju et al. 2002; Coblentz et al.…”

“…After synapse formation, this protein is normally downregulated but remains expressed in specific regions that are thought to retain some degree of cell plasticity (Coblentz et al 2003). Although GAP 43 is nearly absent in normal adult retina (Kapfhammer et al 1994), this developmentally regulated protein can be re-expressed or increased in various types of damage such as axon injury and ischaemia (Doster et al 1991;Ju et al 2002;Coblentz et al 2003;Sethi et al 2005). In addition, while GAP 43 IR was found to be maximal in the IPL immediately following illumination using white light (12 000 lux) for 8 days, these levels were also maximal in regenerating outer photoreceptor segments of rats maintained in total darkness for 10 days (Lopez-Costa et al 2001).…”

Quantitative and Qualitative Analysis of Proteins in Rat Peripheral Nerves Predegenerated for 7 Days

“…Perhaps among fractions with molecular weights from 25.5 kDa to 50.4 kDa which increases the number of subfractions, there are some proteins building the peripheral myelin sheet. The molecular weight of the main protein in peripheral myelin P 0 is 30 kDa and LG1 -25 kDa, as well as Wolfgram proteins -52 kDa and 55 kDa and two izoforms of CNP -46 kDa and 48 kDa 11,16,18,21,22,39 . Myelin sheet proteins do not possess neurotrophic properties but as components of newly formed myelin, they might be able to influence the remyelinization process of regenerating nerve fibres.…”

“…The repeated increase of this protein expression occurs after breaking continuity of the nerve. GAP-43 is responsible for the polymerisation of actin 18 . Recently, GAP-43 has also been implicated in the regulation of synaptic transmission and plasticity in long-term potentiation 15 .…”

What can we learn about stroke from retinal ischemia models?

“…One of the prominent molecular changes found in retinal ischemic injury, as well as optic nerve crush and transection, is the transient increase in growth-associated factor 43 (GAP-43) [29] . Specifically, after ischemic injury GAP-43 was found to be increased in retinal ganglion cells (RGCs) at 3 and 7 days following reperfusion [30] . GAP-43 is most recognized for its expression during CNS synaptogenesis: it is a membrane-associated protein which is up-regulated in neuronal growth cones, but which is down-regulated after synaptogenesis in almost all brain regions, except for those few which preserve plasticity [31] .…”