Abstract
Abstract: :
Purpose: Our laboratory has recently demonstrated that a well-regulated T cell-mediated immune response reduces the loss of retinal ganglion cells (RGCs) following glutamate insult. The ability to mount a T cell-mediated protection was correlated with resistance to autoimmune disease development. Here we examine the effect of immune elements on the ability to cope with glutamate insult to RGCs. Method: In two mouse strains (Babl/c and C57bl/6J) wild type and three types of transgenic mice (nude, B cell KO, and SCID mice) were examined. Following intravitreal injection of glutamate (200 nmoles), some transgenic mice were injected (i.v.) with either splenocytes or B cells from matched wild-type mice. RGC were retrogradely labeled with fluorescent dye, stereotactically applied into the superior culicolus, 72 hours prior to retina excision. The number of surviving RGCs was evaluated 7 days after glutamate application. Results: Injection of glutamate caused loss of RGCs which was significantly higher in C57bl/6J (EAE-susceptible) mice than in balb/c (EAE-resistant) mice. Moreover, unlike T-cell-deficient balb/c mice, T-cell-deficient C57bl/6J mice did not show a higher RGC loss compared to their matched wild-type controls. Also, survival after glutamate toxicity in C57bl/6J mice was significantly higher in B cell KO mice than in the wild type. This improvement was diminished by replenishing the B cell KO mice with B cells from the wild-type, suggesting that at least in susceptible strains, B cells have a negative effect on the outcome of glutamate toxicity. Interestingly, for SCID mice devoid of both T cells and B cells, the outcome in the susceptible strain was better than in the wild-type. However, in the resistant strain the results in the SCID were worse than in the wild-type and similar to those of SCID C57bl/6J mice. Conclusion: These results suggest for the first time that the survival of neurons following glutamate toxicity is critically affected by immune potency. In a susceptible mouse strain, possessing a poor ability to control an autoimmune response, the outcome of glutamate insult can be improved by complete immune deficiency. Conversely, in resistant strains with a high ability to control T cell mediated protective autoimmunity, the ability to cope with glutamate toxicity is significantly reduced in the absence of adaptive immunity. The take-home message is that a well-controlled immunity is worth augmenting but a malfunctioning immunity is destructive and should be modulated.