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PURPOSE: Previously, immunization of rats with ocular antigens induced retinal ganglion cell (RGC) degeneration. We investigated the effect of immunization with glial cell line-derived neurotrophic factor (GDNF) or GDNF in combination with heat shock protein 27 (GDNF+HSP) on RGCs and other retinal cells. METHODS: Rats were immunized with GDNF or GDNF+HSP. After 4 weeks, retinas were stained with Brn-3a and NeuN to quantify RGCs. GFAP and vimentin staining were used to investigate macroglia. Microglia were marked with Iba1 and ED1. Amacrine cells were labeled with parvalbumin and ChAT. Photoreceptors were evaluated with rhodopsin and opsin staining and bipolar cells with PKCα and recoverin. For these cell types, Western blotting was also performed. RESULTS: Retinas of immunized animals showed a significant loss of Brn-3a+ and NeuN+ RGCs. No significant changes could be observed in regard to macroglia. An increase in Iba1+ microglia was detected in both groups, but little change in regard to activated microglia. A loss of cholinergic amacrine cells was seen in the GDNF+HSP group by immunohistochemistry and in both groups via Western blot analysis. AII amacrine cells, bipolar cells, and photoreceptors were not affected. CONCLUSIONS: Immunizations led to loss of RGCs and cholinergic amacrine cells and a strong increase in microglial cells. Our data suggest that RGC loss is the consequence of immunization with GDNF. Astrocyte activity and its neuroprotective effects seem to be inhibited by GDNF immunization. We presume more complex interactions between GDNF and HSP27 because no additive effects could be observed.