In contrast, C2C12 myoblasts adhered to, spread and proliferated on all matrices

l eyes from DBA/2J mice that develop very elevated IOPs. TNF- may be a strong participant in this process. Recent evidence suggests that TNF- promotes neurodegeneration through inhibition of IGF-1 pathways. By inhibiting essential components of IGF-1 downstream regulators, such as PI3K, low non-toxic concentrations of TNF- secreted by reactivated glial cells may indirectly trigger the death of neurons. Some studies have shown increased levels of TNF- in glaucomatous retinas obtained at autopsy. Tezel 19 / 24 Progenitor Cells Expressing IGF-1 on Retinal Ganglion Cell Survival et al. found that up-regulation of TNF- and its receptor-1 in glaucomatous retina suggesting that TNF–mediated cell death is involved in the neurodegeneration processes in glaucoma. Increased production of TNF- by glial cells in glaucomatous eyes may therefore lead to death of RGCs through direct activation of the apoptotic cell death cascade. Tezel and Wax found that glial cell secrete TNF- as well as other noxious agents such as nitric oxide into co-culture media, which in turn facilitate apoptotic death of RGCs. Their findings suggest that inhibition of TNF- secreted by reactivated glial cells may provide a new therapeutic target for neuroprotection in the treatment of glaucomatous optic neuropathy. IGF-1 can also reduce the production of pro-inflammatory cytokines through suppression of NF-B signaling pathway, thus inhibiting the cascade of pro-inflammatory cytokines. Our results indicate that hNPIGF-TD cells reduce production of other chemokines, such as MCP-1, suggesting that hNPIGF-TD cells can influence chemokine production and decrease recruitment of peripheral leukocytes. The levels of messages for pro-inflammatory cytokines, TNF- and IL-1 were quite low in the glaucomatous mice transplanted with hNPIGF-TD cells. An interesting observation involves the effects of hNPs in absence of any IGF-1 on experimental glaucoma. Although these eyes exhibited loss of RGCs and axonal damage similar to those observed in the saline injected microbead group, hNPs did influence the message for inflammatory factors but had a modest anti-angiogenic effect by affecting VEGF levels. It is likely that the combination of IGF-1 and hNPs may be important for maintaining an anti-inflammatory and anti-angiogenic milieu in the setting of glaucoma. In summary, this study describes the application of a specialized neuronal progenitor cells line that spontaneously hones in to the inner retinal layers as a vehicle for local production and delivery of a desired NTF. The aim of neuroprotection for PTK/ZK cost glaucoma therapy is to use agents that prevent or delay RGC PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19783938 death, as well as rescue or even support regeneration of already compromised RGCs. Delivery of NTFs does not have be executed in a non-specific, gunshot manner. Low-dose targeted delivery of NTFs such as IGF-1 released transplanted cells is adequate to confer meaningful neuroprotection. We have shown that hNPs are good cell candidates for RGC rescue as they can spontaneously penetrate and integrate into the host RGC and nerve fiber PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19784385 layers where they locally synthesize and secret biologically active IGF-1. Our findings from the co-culture systems also show that IGF-1 has significant positive effects on enhancing RGC survival rate and neurite growth. Transplantation of hNPIGF-TD cells effectively protects survival of host RGCs after microbead injection. These findings have provided experimental evidence and form the basis for applying cell