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Patrick A Scott, Henry J Kaplan, Maureen A McCall; Prenatal Exposure to Curcumin Protects Rod Photoreceptors in a Transgenic Pro23His Swine Model of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3611.
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© ARVO (1962-2015); The Authors (2016-present)
Expression of mutant rhodopsin alters the morphology and function of rod photoreceptors in transgenic (Tg) Pro23His (P23H) mini-swine in early postnatal retinas (IOVS:2014;55:2452-2459). Loss of rod photoreceptors appears to facilitate degenerative changes in cone photoreceptors in TgP23H mini-swine (IOVS:2014;55:2460-2468) and in human retinitis pigmentosa (RP) patients. Curcumin has been shown to be a neuroprotective agent. The purpose of this study was to test the hypothesis that a daily dietary supplement of curcumin in the mother’s feed might delay morphological changes that occur to rod photoreceptors in TgP23H mini-swine late in embryonic development.
Domestic sows were inseminated with semen from a TgP23H mini-swine founder. Curcumin (100 mg/Kg body weight) was added to the daily diet of one sow during gestation from embryonic (E) day 80 - E112. A second control sow was fed the same diet without curcumin. At E112, two days prior to parturition, sows were euthanized and their embryos (Wild Type (WT), N=8; WT Treated (Tx), N= 2; Tg, N=8; Tg Tx, N=4) harvested and their eyes enucleated and prepared for morphological evaluation. All embryos were genotyped by PCR.
Curcumin supplementation had a significant neurotrophic effect on Tg swine embryonic rod photoreceptors. Mean ONL (outer nuclear layer) thickness was similar between all WT and Tx Tg swine embryos (43.74 um ± 0.58 vs 41.06 um ±1.23; mean ± SEM, respectively). In contrast, the ONL of untreated Tg swine embryos was significantly thinner (35.35 um ± 0.80; p value <0.05). Rhodopsin expression (1D4 antibody) was similar in WT and Tx Tg swine embryos and was confined to rod outer segments. In untreated Tg, rhodopsin expression was mislocalized to the ONL. At the electron microscopic level, WT and Tx Tg swine embryo photoreceptor morphology was similar, whereas untreated Tg rods lacked outer segments and spherules.
Our results support the idea that curcumin can act as a neuroprotective agent to prevent abnormal morphological changes that occur early in rod photoreceptor degeneration in this TgP23H swine model of RP. Further studies are warranted to define the duration of neuroprotection. Because the swine retina has several similarities to primate, this model and curcumin neuroprotection may be valuable to understand the molecular mechanism underlying curcumin neuroprotection in RP.
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