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Arunkumar Ranganathan, Eric Kunz, M Elizabeth Hartnett, Paul S Bernstein; Unexpected susceptibility to Oxygen-induced Retinopathy (OIR) in β,β-carotene-9',10'-oxygenase 2 (BCO2) Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1662.
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Retinopathy of prematurity (ROP) is one of the leading cause of juvenile blindness worldwide. Premature infants at risk for ROP are known to be severely carotenoid deficient because these babies miss out on placental transfer of carotenoids from their mother during the third trimester. We, therefore, hypothesized that prenatal maternal supplementation of macular carotenoids prior to pre-term birth could alleviate ROP. In order to study the possible beneficial effect of carotenoids in a mouse model of ROP using oxygen-induced retinopathy (OIR), we used β,β-carotene-9',10'-oxygenase 2 (BCO2) knockout (KO) mice because, unlike wild-type (WT) mice, they can accumulate macular pigments in their retinas in a manner similar to humans.
P7 mouse litters of BCO2 KO mice on a C57BL6/J background along with their nursing mothers, who had been fed with normal chow, were exposed to 75% oxygen for 5 days (P12) in a ProOx model P360 hyperoxia chamber (BioSpherix, Ltd.) to initiate OIR and then returned to room air (21% oxygen) for another 5 days (until P17) for vascular regrowth and neovessel formation. WT C57BL6/J mice fed with normal chow and placed into OIR were used as controls. Retinas recovered from BCO2 KO and WT (n=3) mice/time point were sacrificed at P12, P13, P14, and P17 were used for lectin-stained retinal whole mounts. Retinas received a score that reflected what percentage of the total retina was the central avascular area (AVA) from manual selection by a grader using Image J (v. 2018).
WT mice at P17 show AVA (5.5 ± 1.7), but surprisingly we did not observe AVA in BCO2 KO mice at P17. At P12, there was higher AVA in BCO2 KO (24.5 ± 0.5) compared to WT mice (21.0 ± 1.0), but the AVA in BCO2 KO mice decreased rapidly at P13 (20.2 ± 1.9) and P14 (9.6 ± 2.3) compared to WT mice (20.6 ± 1.7 and 18 ± 2.1 respectively). BCO2 KO mice show greater vascular regrowth compared to WT mice. The AVA values in BCO2 KO mice were statistically significant (p ≤ 0.05) at P12, P14, and P17 compared to WT.
β,β-carotene-9',10'-oxygenase 2 (BCO2) appears to act as an OIR modulator because all BCO2 KO mice showed enhanced revascularization relative to WT mice. We are continuing to explore the biochemical mechanism underlying BCO2-mediated protection against OIR.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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