Functional status influences the ability of Schwann cells to support adult rat retinal ganglion cell survival and axonal regrowth

Abstract

Properties of Schwann cells (SC) within the environment of the peripheral nerve can differ depending on their state of differentiation (e.g., quiescent, proliferating or mature SCs). In the present study we have tested the efficacy of SCs in different functional states to promote adult rat retinal ganglion cell (RGC) survival and neurite growth. We have used culture conditions which allowed regenerating retinal axons to contact SCs (1) as quiescent SCs that had not been in contact with axons, (2) as SCs that had been proliferating in contact with neurites, and (3) as mature SCs which had myelinated axons and deposited basal lamina around the axon-SC unit. Both proliferating and mature SCs were activated, i.e., were removed from axonal contact by inducing Wallerian degeneration, 2–3 days prior to testing their ability to support neuronal survival and neurite growth. Activated SCs, (derived from either proliferating or mature SCs) supported adult rat RGC survival and axonal regrowth significantly better than quiescent SC monolayers. Conditioned media (CM) derived from corresponding SC preparations (quiescent, proliferating, or mature SCs) supported short-term survival of RGCs and neurite outgrowth on defined substrata. A dissociation of substrate adsorbable neurite-promoting and nonadsorbable neurotrophic factors could be observed. The neurite-promoting activities found in CM were trypsin and heat sensitive, suggesting that the active component(s) is protein(s). None of the CM tested was able to support adult rat RGC survival and axonal growth as effectively as activated SCs (either proliferating or mature SCs). Long-term survival (>4 days) of RGCs in explant cultures were especially dependent on RGC-neurite contact with preactivated SCs; CM derived from corresponding SCs (mature and proliferating SC-CM) were significantly less effective in supporting long-term survival. From these data we conclude that consideration must be given to the functional state of the SCs in experiments designed to utilize SCs in promoting CNS regeneration.