Intravitreal transplants of Schwann cells and fibroblasts promote the survival of axotomized retinal ganglion cells in rats

Abstract

Schwann cells (SCs) are considered one of the major cellular components to maintain the integrity of the peripheral nervous system (PNS) neurons after injury. Intravitreal transplant of peripheral nerves or Schwann cells has been shown to enhance the regenerative ability of retinal ganglion cells (RGCs). In the present study, we compared the effects of intravitreal transplants of Schwann cells and fibroblasts, two major components of peripheral nerves, on the survival of retinal ganglion cells in adult rats after optic nerve (ON) transection. Purified Schwann cells and fibroblasts from neonatal sciatic nerves were injected into the vitreous body of adult rats. Three days after the injection, the optic nerves were transected intraorbitally. After 1 week or 1 month, surviving retinal ganglion cells were retrogradely labelled with Fluoro-Gold (FG) and the number of surviving retinal ganglion cells was counted. The retinas were further processed for 200-kDa neurofilament RT-97 immunohistochemistry. It was found that intravitreally injected- Schwann cells and -fibroblasts delayed the death of axotomized retinal ganglion cells for 1 week. In addition, in the animal group with 1 month survival time after optic nerve transection, those received a larger number of Schwann cells had more surviving retinal ganglion cells and more profusely ramified axonal processes near the optic disc. These findings reveal that both Schwann cells and fibroblasts isolated from the peripheral nerve can promote retinal ganglion cell survival after optic nerve transection, presumably by secreting neurotrophic factors. In addition, the data also demonstrate that Schwann cells could promote intraretinal axonal sprouting. Our findings demonstrate a remarkable glial source of neurotrophic factors with potential clinical applications, as autologous Schwann cells and fibroblasts can be feasibly obtained from peripheral nerves. © 2004 Elsevier B.V. All rights reserved.