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Xiaokun Han, Angelina Jingtong Liu, Eric Kunz, Colin A Bretz, M Elizabeth Hartnett, Haibo Wang; Inhibition of Uncoupling Protein 2 Promotes Postnatal Growth and Physiologic Retinal Vascular Development in a Rat Model of Oxygen Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3638. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Clinical studies find that poor postnatal growth is associated with greater severity of ROP seen as reduced physiologic retinal vascular development (PRVD) in Phase I and increased intravitreal neovascularization in phase II. In our preliminary study, increased uncoupling protein 2 (UCP2), a regulator of energy metabolism and glucose sensor, was found in the hypothalamus, skeletal muscle and retina of rat pups in oxygen induced retinopathy (OIR) model compared to room air raised pups at the same developmental age. We tested the hypothesis that inhibition of UCP2 increases postnatal growth by increasing food intake and reducing energy expenditure and promotes PRVD in the rat model of OIR.
Within 4-6 hours of birth, S prague-Dawley dams and pups (male and female) were placed into an Oxycycler that cycled oxygen between 50% and 10% oxygen every 24 hours. Rat pups in the OIR model received intraperitoneal injections of genipin (20 mg/kg), an UCP2 inhibitor, or equal volumes of PBS every other day beginning at p3 and extending through p13. The injections were performed at the end of the 50% cycle. Pup weights and rectal temperatures reflecting body energy expenditure, were measured during the times when injections were given. At postnatal day 14 (p14), overall energy intake was determined by pup blood glucose. Pups were then euthanized and evaluated to assess PRVD. At p14, retinal flat mounts were prepared, stained with isolectin and imaged with fluorescent microscopy. Avascular retinal area to total retinal area (% AVA) was measured by ImageJ to assess PRVD. Statistics were performed using two-tailed Student’s t-test.
Compared to PBS-treated pups, genipin-treated pups had a significantly greater weight gain from p3 before injection to p14 (6.12±0.27 grams vs. PBS 5.14±0.39 grams, p=0.05, n=9) with lower rectal temperature (31.1±0.18°C vs. PBS 31.87±0.32°C, p=0.049, n=9) and a trend in higher blood glucose (112.89±4.49 mg/dl vs. PBS 101.22 ± 4.50 mg/dl, p=0.085, n=9), and less % AVA (31.77±3.10 vs. PBS 45.52±4.61, p=0.025, n=9).
Inhibition of UCP2 by genipin in the OIR model promoted postnatal growth, reduced energy expenditure (measured by lower temperatures), had a trend toward increased energy intake, measured by serum glucose, and improved PRVD, as seen by reduced AVA.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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