Abstract
Studies have suggested an involvement of the immune system in glaucoma. Hence, a rat experimental autoimmune glaucoma model (EAG) was developed to investigate the role of the immune response. Here, we transferred this model into mice. Either 0.8 mg/mL of the optic nerve antigen homogenate (ONA; ONA 0.8) or 1.0 mg/mL ONA (ONA 1.0) were injected in 129/Sv mice. Controls received sodium chloride. Before and 6 weeks after immunization, the intraocular pressure (IOP) was measured. At 6 weeks, retinal neurons, glia cells, and synapses were analyzed via immunohistology and quantitative real-time PCR (RT-qPCR). Additionally, optic nerves were examined. The IOP stayed in the normal physiological range throughout the study (p > 0.05). A significant reduction of retinal ganglion cells (RGCs) was noted in both immunized groups (p < 0.001). Remodeling of glutamatergic and GABAergic synapses was seen in ONA 1.0 retinas. Furthermore, both ONA groups revealed optic nerve degeneration and macrogliosis (all: p < 0.001). An increase of activated microglia was noted in ONA retinas and optic nerves (p < 0.05). Both ONA concentrations led to RGC loss and optic nerve degeneration. Therefore, the EAG model was successfully transferred from rats to mice. In further studies, transgenic knockout mice can be used to investigate the pathomechanisms of glaucoma more precisely.
Highlights
Glaucoma is a progressive neuropathy with changes in the optic nerve head, gradual retinal ganglion cell (RGC) death, and visual field loss [1]
Since a disruption of axonal transport in RGCs seems to be play a role in glaucoma, we aimed to examine different types of synapses in this new model
6 weeks after immunization, the intraocular pressure (IOP) was not altered in both optic nerve antigen homogenate (ONA)-immunized groups (ONA 0.8: 13.90 ± 0.38 mmHg, p = 0.053; ONA 1.0: 13.31 ± 0.60 mmHg, p = 0.18) in comparison to the control animals (11.02 ± 0.52 mmHg)
Summary
Glaucoma is a progressive neuropathy with changes in the optic nerve head, gradual retinal ganglion cell (RGC) death, and visual field loss [1]. An elevated intraocular pressure (IOP) is the main risk factor, IOP-unrelated pathomechanisms occur. Since this disease is multifactorial, appropriate models mimicking possible pathological pathways are needed. Rats were immunized with ocular antigens, such as heat shock proteins (HSPs) or an optic nerve antigen homogenate (ONA). This led to a loss of RGCs and optic nerve degeneration [2,3,4]. To evaluate the extent of cellular infiltration, longitudinal cryo-sections of optic nerves were stained with H&E. Three images of each optic nerve section (anterior, medial, and posterior) were taken with an Axio Imager M1 microscope at a 400x magnification (six sections per animal)
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