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Christina Casola, Sabrina Reinehr, Sandra Kuehn, Bernhard Spiess, Burkhard Dick, Stephanie C Joachim; Neuronal cell loss in an autoimmune glaucoma model after immunization with GDNF and HSP27. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2459.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is a vision threatening disease. Different possible pathogenic factors have been described, including the involvement of the immune system. Previously, immunization with glaucoma related antigens, like heat shock proteins (HSP), induced retinal ganglion cell (RGC) degeneration. The purpose of this study was to investigate RGC death and alterations in macroglia, amacrine cells and photoreceptors after immunization with glial cell-derived neurotrophic factor (GDNF) or GDNF in combination with HSP27.
Rats were immunized with GDNF and GDNF+HSP27. Control animals (Co) received sodium chloride (n=4-5/group). After 4 weeks cross-sections of the retina were stained with Brn-3a and NeuN to quantify RGC density. GFAP and vimentin staining was used to investigate macroglia and was confirmed by Western Blot. Amacrine cells were labelled with parvalbumin and photoreceptors with rhodopsin and opsin. Cell counts and staining area analysis were done using ImageJ software. Statistical analysis was performed using Student’s t-test.
Retinas of immunized animals showed a significant loss of Brn-3a+ RGCs (Co: 29.72±4.94 cells/mm; GDNF: 20.01±6.2 cells/mm; p=0.025; GDNF+HSP27: 23.15±1.78 cells/mm; p=0.04) or NeuN+ RGCs (Co: 30.08±3.14 cells/mm; GDNF: 22.5±6.01 cells/mm; p=0.037; GDNF+HSP27: 23.22±1.54 cells/mm; p=0.005). In the GDNF group the GFAP+/vimentin+ area was significantly increased compared to Co (GFAP: p=0.00005; vimentin: p=0.007). No changes in macroglia staining could be observed in the GDNF+HSP27 group (p>0.05). A loss of amacrine cells was detected with parvalbumin staining solely in the GDNF+HSP27 group (Co: 32.91±19.41 cells/mm; GDNF: 34.26±15.18 cells/mm; p=0.55; GDNF+HSP27: 27.75±14.99 cells/mm; p=0.04). Photoreceptors were not affected in both groups.
Immunization with GDNF as well as the combination of GDNF+HSP27 led to a significant RGC loss. In the GDNF group an activation of macroglia was observed, but no further damage of retinal cells. In contrary, we detected no macroglia activation in the GDNF+HSP27 group, but a loss of amacrine cells. We propose, that an inhibition of glia cell activity after immunization with GDNF in combination with HSP27 occurs. Therefore, the deeper retinal layers are more affected.
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