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Lei Xu, Huiming Xia, John D Ash; Metformin protects photoreceptors in mice with the PDE6bRd10 mutation and protects RPE in mice treated with sodium iodate. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5751.
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We have previously reported that metformin, an agonist of AMPK, can protect photoreceptors from light damage and it is through increase mitochondrial DNA copy number which boost robust response of photoreceptors under stress condition. The goal of this study was to determine whether metformin can preserve photoreceptors in inherited retinal degeneration model rd10 mice and metformin’s effect on RPE function using sodium iodate induced RPE cell death model.
Rd10 mice were given once per day subcutaneous doses of metformin beginning at postnatal day 13 (P13). Control Rd10 mice were given saline. We compared the rate of degeneration in metformin treated mice with mice given saline. To study metformin-induced protection of RPE, BALB/cJ mice were pretreated for seven days with metformin or saline. Mice were then given a single intraperitoneal injection of Sodium iodate in a range of doses between (30 mg/Kg and 35 mg/Kg). Retina function was measured by electroretinograph (ERG) and retinal structure was measured by Spectral domain Optical Coherence Tomography (SD-OCT) imaging. Western blots, real time PCR and immunohistochemistry were used to investigate mechanisms. All procedures with animals were conducted in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
Systemic metformin treatment led to activation of AMPK in the retina, and preserve the photoreceptors in RD10 mice as determined by SD-OCT imaging and histology. Metformin also protected RPE from sodium iodate induced death.
Metformin induced neuroprotection of photoreceptor and RPE. Our date suggest that metformin or other drugs targeting AMPK should be developed to prevent or reduce blindness caused by inherited mutations or degeneration of RPE.
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