%0 Journal Article
%T Roles of PI3K and JAK pathways in viability of retinal ganglion cells after acute elevation of intraocular pressure in rats with different autoimmune backgrounds
%A Yao Huang
%A Zhiwei Li
%A Ningli Wang
%A Nico van Rooijen
%A Qi Cui
%J BMC Neuroscience
%D 2008
%I BioMed Central
%R 10.1186/1471-2202-9-78
%X Similar to what was previously observed, significantly more RGCs were lost in Lewis than F344 rats 3 weeks after acute IOP elevation. As in SPD rats, inhibition of the PI3K/akt or JAK/STAT pathway increased the loss of RGCs in both F344 and Lewis rats. Removal of macrophages in the eye by clodronate liposomes reduced RGC loss due to pathway inhibition in both strains.This study demonstrates that following acute IOP elevation 1) PI3K/akt and JAK/STAT pathways mediate RGC survival in both F344 and Lewis rats, 2) autoimmune responses do not influence the functions of these two pathways, and 3) PI3K/akt and JAK/STAT pathway inhibition-dependent activation of macrophages is detrimental to RGCs.Loss of retinal ganglion cells (RGCs) occurs in many pathological situations, and glaucoma is one of the common diseases that lead to RGC loss. A common feature of glaucoma is elevation of intraocular pressure (IOP) that causes progressive axonal degeneration and loss of RGCs. As acute glaucoma is characterised by rapid increase in IOP, acute IOP elevation paradigm in rodents has often been used to study acute IOP elevation-induced retinal ischemic/reperfusion injury and the possible mechanisms underlying acute glaucoma-associated RGC injuries [1-5].It is known that immune responses can influence neuronal survival after injury. Whereas ample evidence pointed to a damaging effect of inflammatory responses of macrophages and T-cells after CNS injury and in autoimmune diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) [6-13], T-cell dependent RGC protection in response to IOP elevation has also been reported in EAE-resistant Fischer 344 (F344) but not EAE-vulnerable Lewis rats [14]. In our earlier study, we found that macrophages, which are another major component of the autoimmune system, responded differently to IOP elevation or optic nerve (ON) injury between F344 and Lewis rats, and such differences led to different extents of RGC survival afte
%U http://www.biomedcentral.com/1471-2202/9/78