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Sara Cristina da Piedade Gomes, Sabrina Reinehr, Caroline Julia Gassel, Burkhard Dick, Stephanie C Joachim; Novel treatment approach via complement factor C5 inhibition in an Experimental Autoimmune Glaucoma model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4860.
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Glaucoma is associated with a loss of retinal ganglion cells (RGCs) and their axons. In an intraocular pressure-independent glaucoma model, RGC loss and optic nerve degeneration occurred 4 weeks after immunization with an optic nerve homogenate antigen (ONA). Additionally, an activation of the complement system in retinas and optic nerves was observed prior to degeneration. Here, we investigated whether the intravitreal administration of a monoclonal antibody (BB5.1) against complement factor C5 can prevent RGC loss.
Rats were immunized with ONA and compared to controls (Co). In one of the eyes of the ONA immunized animals, the antibody BB5.1 (Hycult Biotech) was injected. Two different concentrations were compared (15 μmol: ONA+C5-I; 25 μmol: ONA+C5-II). Intraocular pressure (IOP) was measured weekly (n=10/group). After 6 weeks, optical coherence tomography (OCT) was performed (n=4-8/group). Subsequently, cross-sections of the retina were stained with the RGC marker Brn-3a and the apoptosis marker cleaved caspase 3 (n=6-8/group). In addition, we carried out a quantitative real-time PCR (qRT-PCR) to evaluate expression levels of Pou4f1 and Bax/Bcl2 mRNA (n=4/group).
IOP remained within the normal range in all groups (p>0.05). There were also no changes regarding the retina thickness between the groups (p>0.05). The ONA group showed a significant lower number of RGCs (20.8±4.6 cells/mm, p=0.001) compared to Co (49.7±2.0 cells/mm), while eyes from the ONA+C5-I (36.3±5.4 cells/mm, p=0.22) and ONA+C5-II (39.4±7.3 cells/mm, p=0.5) groups showed no significant difference to Co. We confirmed this with qRT-PCR, in which we identified lower Pou4f1 mRNA levels in the ONA eyes compared to Co (0.24-fold expression; p=0.03). There was no significant difference between Co and the ONA+C5-I (0.45-fold expression, p=0.09) and ONA+C5-II groups (0.84-fold expression, p=0.3). There was also no difference in the proportion of RGC undergoing apoptosis between the groups (p>0.05).
Immunization with ONA leads to a loss of RGC in this model. Our results indicate that intravitreal administration of a monoclonal antibody against the complement factor C5 prevents this RGC loss via the inhibition of MAC formation. These approach might be a suitable new glaucoma treatment.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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