Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats

TLDR

The enhanced survival of axotomized retinal ganglion cells in peripheral‑nerve‑grafted retinas appears limited to the first few weeks after injury, suggesting that neuronal viability depends on a spectrum of differently timed influences, including early diffusion of graft‑derived molecules and later complex interactions with graft components. The study investigated whether extrinsic influences introduced by apposing a peripheral nerve segment at the time of optic nerve transection could affect the survival and growth of axotomized retinal ganglion cells in adult rats. Survival and axonal regrowth were assessed by morphometric analysis, neuroanatomic tracers, and immunologic cell markers over a period from 15 days to 9 months post‑axotomy. Axotomy without a graft caused over 90 % retinal ganglion cell death within one month, whereas grafting a peripheral nerve segment increased survival 2–4 fold between one and three months and enabled about 20 % of surviving cells to regrow axons into the graft, with axon‑bearing cell densities remaining stable despite overall cell loss.

Abstract

To investigate the role of extrinsic influences on the survival and growth of axotomized retinal ganglion cells (RGCs) in the mature mammalian CNS, both optic nerves (ONs) of adult rats were transected intraorbitally and, on one side, replaced by an autologous segment of peripheral nerve (PN) that had been left unconnected distally. The survival of RGCs and the regrowth of their cut axons into the PN grafts were assessed using morphometric techniques, neuroanatomic tracers, and immunologic cell markers to identify and count RGCs at times ranging from 15 d to 9 months. It was observed that (1) in the absence of a PN graft, more than 90% of the RGCs died by 1 month after axotomy; (2) between 1 and 3 months after axotomy, survival of RGCs in the PN-grafted retinas was enhanced 2-4-fold; (3) nearly 20% of the surviving RGCs regrew lengthy axons into the grafts; and (4) although the density of surviving RGCs in PN-grafted retinas decreased significantly between 1 and 3 months after axotomy, the densities of RGCs with axons extending into the graft remained relatively stable. These results confirm that in the adult rat retina, neuronal death is a major effect of axotomy near the cell soma. Although such lesions lead to the degeneration of many RGCs, we show that extrinsic influences introduced by the apposition of a PN segment at the time of severing the ON can rescue a substantial number of these neurons. Because the enhanced survival of many axotomized RGCs in the PN-grafted retinas appears to be limited to the first few weeks after injury, while those of RGCs that regenerate axons into the grafts do not show a parallel decline, it is possible that, in these experiments, neuronal viability depends on a spectrum of differently timed influences that may include the early diffusion of critical molecules arising from the graft and the subsequent establishment of more complex interactions with graft components.