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Enrique J De La Rosa, Alberto M Hernandez-Pinto, Javier Vicente-Tejedor, Laura Ramírez, Eduard Ayuso, Patricia Boya, Catalina Hernandez- Sanchez, Fátima Bosch, Pedro de la Villa; Visual decline in aged mice is delayed by proinsulin.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4392.
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© ARVO (1962-2015); The Authors (2016-present)
Visual decline is normally associated to the aging process. We search for cellular and molecular processes associated to normal aging. In addition, we have previously shown that human proinsulin (hPi) delays vision loss, as determined by electroretinography (ERG), and retinal degeneration, as determined by photoreceptor counting, in the rd10 mouse and the P23H rat models of Retinitis Pigmentosa. Our aim is to reveal additional potential benefits of a hPi-based treatment in the aged retina.
Wild type mice (C57BL/6) were studied at 3- to 22-months of age. Retinal structure was determined in cryo-sections. Pro-inflammatory gene expression was characterized by RT-qPCR. Insulin resistance was established in organotypic retinal cultures, measuring AKT phosphorylation by western blot. In addition, mice were treated by intramuscular injection of adeno-associated viral vector, either empty (AAV-Ø) or encoding hPi (AAV-hPi) at six month of age. Visual function was evaluated by ERG in 9- to 18-month old animals.
In comparison with young adult animals, visual function decline was evident at 12 months of age, with a 30-40% reduction in the amplitude of several ERG waves. In parallel, TNF-α gene expression increased 2-4 fold, and cultured retinas did not longer show AKT phosphorylation in response to insulin. AAV-mediated expression of hPi delayed 3 to 6 month the onset of visual decline at mid-age.
Retinal aging involves processes found in normal and precocious brain aging, namely low level of chronic inflammation, insulin resistance and functional decline. Neuroprotection with hPi provides a potential treatment to maintain visual quality under different physiopathological conditions, including aging.
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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