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Hsin-Hua Liu, Jeremy M Sivak, Karsten Gronert, John G Flanagan; Protective Effects of Lipoxins A4 and B4 on the Inner Retina in a Chronic Mouse Model of Ocular Hypertension. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6126.
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To investigate the role of lipoxins A4 (LXA4) and B4 (LXB4) in mitigating inner retinal injury in a mouse model of chronic ocular hypertension. We previously reported a neuroprotective effect of LXA4 and B4 in vitro and for LXB4 in a chronic rat model of ocular hypertension.1
Chronic ocular hypertension was induced in male C57BL/6 mice (8 weeks) using a monocular circumlimbal suture. From week 5, they were randomly treated with either vehicle (phosphate-buffered saline), LXA4 or LXB4 (0.1 µg/ µL, locally and systemically, every other day, n = 10 for each group). Intraocular pressure (IOP), retinal function (electroretinogram) and structure (optical coherence tomography) were measured weekly in all groups for 12 weeks. At the end of 12 weeks, animals were euthanized and retinal ganglion cell (RGC) counts were evaluated following RBPMS immunostaining (flat-mount).
LXA4 and LXB4 had no effect on IOP. At week 12, RGC function (pSTR) was reduced by -27.8 ± 2.1% in the vehicle group, -24.0 ± 1.3% in the LXA4 group (p = 0.29) and -20.9 ± 1.0% in the LXB4 group (p < 0.01). Retinal nerve fiber layer (RNFL) thickness was reduced by -25.2 ± 1.4% in the vehicle group compared to -23.8 ± 1.6% in the LXA4 group (p > 0.99) and -20.9 ± 1.0% in the LXB4 group (p < 0.05). Loss of RGC in the vehicle group was -17.2 ± 1.2%, -14.1 ± 1.0% for the LXA4 group (p = 0.13) and -12.2 ± 0.9% for the LXB4 group (p < 0.01).
LXB4, unlike LXA4, had marked neuroprotective actions in a preclinical mouse model of ocular hypertension, through a mechanism independent of IOP. LXB4 neuroprotective actions in a mouse model of ocular hypertension are consistent with our recent findings in a rat model of glaucoma.1 More importantly, they identify distinct actions for endogenous lipoxins, LXA4 and LXB4, in the retina and optic nerve head. LXB4 is a potential therapeutic target for the treatment of the neurodegenerative disease glaucoma.1. Livne-Bar I, Wei J, Liu HH, et al. Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury. J Clin Invest. 2017.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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