Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to favorable stimuli.

No abstract

We have determined whether chondroitin sulphate (CS) glycosaminoglycans are sufficient to direct a selective inhibition of neurite growth from ventral temporal (VT) but not from dorsal nasal (DN) retina in mouse embryos; this may underlie the formation of axon divergence in the optic chiasm. Explants from the retinal region of embryonic day-14 mouse were grown on a laminin-polylysine substrate near to a circular spot coated with CS. In control cultures, in which no CS was added to the spot, both VT and DN retinal neurites grew extensively into the coated territory. When presented with spots coated with 10 mg/ml CS, neurite growth from the VT retina into the CS territory was dramatically reduced but that from the DN retina was not significantly affected. The selective inhibition to VT neurites was completely abolished by treatment with chondroitinase ABC, indicating a specific contribution of CS glycosaminoglycan in this regionally specific behaviour. This differential behaviour was not observed in explants presented with a lower or higher concentration of CS or in explants grown on substrate coated with a different laminin concentration. Thus, a critical ratio of CS to laminin seems to be essential to induce this differential behaviour in retinal neurites towards contact with CS. Furthermore, this behavior was not observed in explants cultured directly on a CS-rich substrate, suggesting that contact with growth-promoting molecules is necessary for the selective responses of retinal neurites during subsequent contact with CS. We concluded that CS glycosaminoglycan is sufficient to drive selective inhibition of VT but not DN neurites and that, together with a critical combination of growth-promoting factors, it may control the axon divergence process at the mouse optic chiasm.

Lens damage has been demonstrated to promote axonal regeneration of retinal ganglion cells. Various mechanisms associated with this enhancement have been proposed, including macrophage recruitment and stimulatory factors from the lesioned lens. Lens epithelial cells, which become activated as a result of injury, are another potential stimulus. A recent study of co-culturing lens epithelial cells adjacent to retinal explants without direct contact showed that neurites were attracted to grow towards them. We explored the ability of lens epithelial cells to act as a favorable substrate for ganglion cell axonal regeneration, by culturing retinal explants on top of a lens epithelial cell layer, as well as in vivo by transplanting freshly isolated lens epithelial cells to the cut optic nerve. Retinal explants cultured on lens epithelial cells regenerated more and longer neurites than those cultured on either an acellular substrate or a substrate of corneal cells, while lens epithelial cells transplanted to the optic nerve stimulated axons to regenerate in close association with them.