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E.Y. P. Cho, W.K. Wong; Transient Induction of Heat Shock Protein 27 in Axotomized Retinal Ganglion Cells, and Their Sustained Up–regulation in Regenerating Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):189.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The small heat shock protein HSP27 is induced or up–regulated in some neurons after injury where they may be associated with neuroprotective functions. Little is known, however, of the role played by HSP27 in regeneration, especially in the central nervous system. In the retina, expression of HSP27 by retinal ganglion cells (RGCs) has been observed after optic nerve (ON) injury and in glaucoma. In this study, we have compared the expression of HSP27 in axotomized RGCs which are stimulated to sprout axon–like processes by intravitreal transplantation of a peripheral nerve (PN), or when they undergo axonal regeneration into a PN grafted to the ON, to axotomized cells which are not stimulated to regenerate. Methods:The ON of adult golden hamster was transected at 2mm from the eyeball in all groups. In one group, a 2mm PN was implanted into the vitreous to stimulate sprouting of axon–like processes from RGCs. In another group, a long PN was apposed to the cut ON to induce axonal regeneration into the graft. Two control groups were used for comparison, one with implantation of a non–viable PN, and the other without any intravitreal graft. Expression of HSP27 in the whole–mount retina from 3 to 56 days post–transection (PT) was performed by immunostaining with an anti–HSP27 antibody. The number as well as soma area of the labelled cells was quantified. Results: HSP27 was localized to astrocytes and blood vessels but absent in RGCs of normal retina. At 3 and 7 days PT, a number of axotomized RGCs (with a peak number of ∼800) expressed HSP27, but this was almost abolished by 14 days PT in eyes implanted with non–viable PN or without graft. In contrast, RGCs induced to sprout by a viable intravitreal PN sustained the HSP27 expression up to 56 days PT (longest period examined), and the peak number observed was higher than in control groups. Moreover, the intensity of immunostaining increased with post–injury time in the sprouting cells. The axon–like processes growing within the retina as well as their growth cones also possessed high levels of HSP27. RGCs which regrew axons into a PN exhibited a distinct pattern of HSP27 expression in that all regenerating cells except those with very small soma sizes expressed HSP27. Conclusions: The transient expression of HSP27 in axotomized RGCs and their sustained up–regulation in regenerating and sprouting RGCs suggests a functional role in RGC regeneration. Its early induction and continued presence at later phases of regeneration may be associated with both axonal outgrowth and stabilization of the regenerating cell.
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