Expression of ciliary neurotrophic factor activated by retinal Muller cells in eyes with NMDA- and kainic acid-induced neuronal death

PURPOSE. To elucidate the role of retinal Muller cells in N-methyl-D-aspart ate (NMDA)- or kainic acid (KA)-induced retinal damage. METHODS. In experimental eyes, NMDA or KA was injected into vitreous of rat eyes. Immunohistochemistry and western blot analysis were conducted to elu cidate expression and localization of glial fibrillary acidic protein (GFAP ) and ciliary neurotrophic factor (CNTF). In addition, the neuroprotective effects of CNTF were calculated by counting cells in the ganglion cell laye r (GCL) and by measuring the thickness of the various retinal layers. RESULTS. Morphometric analysis of retinal damage in NMDA- and KA-injected e yes showed significant cell loss in the GCL and thinning of the inner plexi form layer (IPL) of the retina, but not of other retinal layers. Immunohist ochemistry demonstrated disappearance and/or decrease in immunoreactivities of calbindin- and calretinin-positive cells and their neurites and upregul ated expression of both GFAP and CNTF in experimental eyes. Western blot an alysis showed an increase in protein expression for CNTF in retinas of expe rimental eyes. Confocal images and sequential localization demonstrated col ocalization of CNTF and GFAP in the inner retinal layer and possibly in Mul ler cells. In addition, pretreatment with CNTF (1 mu g) before the intravit real injection of NMDA (or KA) demonstrated that CNTF has neuroprotective e ffects against NMDA- or KA-induced neuronal death in the retina. CONCLUSIONS. These studies revealed the upregulated expression of CNTF and GFAP in Muller cells in response to NMDA- and KA-induced neuronal death, su ggesting that production of CNTF in Muller cells may be a part of the endog enous neuroprotective system in the retina.