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John G Flanagan, Karsten Gronert, Jeremy M Sivak, Paul Cullen, Hsin-Hua Liu; Deficiency of ALX/FPR2 Deteriorates Inner Retinal Injury in Experimental Chronic Ocular Hypertension. Invest. Ophthalmol. Vis. Sci. 2019;60(9):633.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether inner retinal function and structure exhibit enhanced injury in response to induction of experimental chronic ocular hypetension in lipoxin A4 receptor (ALX/FPR2) knock out mice (ALX/FPR2 KO). We have previously demonstrated that lipoxin A4 is neuroprotective in the murine model.1
Female wild type (WT) C57BL/6 (n=9) and ALX/FPR2 KO (n=8) mice (8 weeks) were treated with monocular circumlimbal suture to induce chronic ocular hypertension. Intraocular pressure (IOP), inner retinal function (electroretinogram, ERG) and structure (optical coherence tomography, OCT) were monitored across 12 weeks. At week 12, retinal samples were collected for histological assessment.
A similar IOP profile was found between the two groups over 12 weeks. For the retinal ganglion cell (RGC) function measured by the ERG, a progressive loss across 12 weeks was observed for both groups. The loss at week 12 was -36.7 ± 1.6% in the WT group and -45.4 ± 2.5% in the ALX/FPR2 KO group (p < 0.01). A comparable finding was noted for the retinal nerve fiber layer (RNFL) thickness by OCT measurement. The loss at week 12 was -29.2 ± 2.0% for the WT group and -40.0 ± 2.8% for the ALX/FPR2 KO group (p < 0.01). Similarly, the loss of RGC density was -25.3 ± 1.6% in the WT group and -34.8 ± 2.3% in the ALX/FPR2 KO group (p < 0.01).
Our data indicate that the loss of ALX/FPR2 leads to exacerbated RNFL defect, RGC dysfunction and apoptosis in chronic ocular hypertension model via a non-IOP related mechanism. This finding suggests that ALX/FPR2 plays a role in mediating inner retinal injury in glaucoma.1. Livne-Bar I, Wei J, Liu HH, Alqawlaq S, Won GJ, Tuccitto A, Gronert K, Flanagan JG, Sivak JM. Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury. J Clin Invest. 2017
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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