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Franklin D Echevarria, Rebecca M Sappington; Loss of interleukin-6 mitigates visual deficits caused by elevated IOP. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2458.
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We demonstrated that IL-6 protects RGCs from apoptosis caused by elevated pressure in vitro. Here, we tested whether loss of IL-6 protects the visual pathway against glaucomatous pathology caused by microbead-induced elevations in IOP. To identify consequences of IL-6 deficiency on glaucomatous pathology, we examined functional visual capacity by measuring changes in VEP waveform, retina to SC transport and visual acuity in 7 month wild-type (WT) and IL-6 knockout (KO) mice.
IOP was elevated in WT and IL-6 KO mice for 8 weeks using the microbead occlusion model. To determine impact on functional visual capacity, we tested RGC response to light using flash-visual evoked potential (fVEP) and measured differences in the VEP waveform. Additionally, visual acuity was measured using optokinetic tracking (OKT) and retina to superior colliculous (SC) transport capability was determined by injecting flourophore-labeled CTB into the vitreous and measuring transported CTB fluorescent intensity in the SC.
Based on IOP measurements, both WT and KO injected with microbeads experienced ~20% elevations in IOP (p>0.05) compared to animals injected with saline. Interestingly, microbead injected IL-6 KO mice show a preserved P1 amplitude, which is 20% greater (p<0.05) compared to microbead injected WT mice. However, microbead injected WT mice experienced a 23% decrease (p>0.05) in visual acuity compared to saline injected WT mice, an effect not seen in microbead injected KO mice. Additionally, microbead injected IL-6 KO mice show decreased deficits in CTB transport compared to microbead injected WT mice.
In constrast to previous in vitro studies, these data suggest that loss of IL-6 protects visual function from glaucomatous pathology in response to elevated IOP in vivo. Overall, these data suggest that IL-6 could be a therapeutic target for glaucoma associated treatment.
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