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Camilla Mohlin, Tanzina Mollick, Kjell Johansson; Human neural progenitor cells are not sufficient to support degenerating photoreceptors in cultured porcine retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3983.
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Neurodegenerative diseases like retinitis pigmentosa, age-related macular degeneration and diabetic retinopathy commonly cause photoreceptor degeneration over time, inducing secondary injuries like gliosis and neuronal remodeling; such mechanisms ultimately lead to impaired vision. Despite intense research, no effective treatment has been found for these disorders. Human neural progenitor cell (HNPC)-derived factors have been shown to protect photoreceptor cells from apoptotic cell death. The current study was undertaken to explore whether HNPC-derived factors could inhibit the degenerative process of photoreceptors in adult porcine retinal explants.
Adult porcine eyes were collected from a local abattoir. The neural retina was gently detached from the pigmented epithelium and peripheral sections were explanted onto a Millicell-PCF 0.4 μm culture plate insert with the vitreal side oriented upwards. Adult porcine retinas were cultured with or without HNPCs as a feeder layer in the bottom of the well. After co-culture for three days the retinas were investigated for cell death by TUNEL assay. Synaptic integrity was assessed by expression of the scaffold protein postsynaptic density protein 95 (PSD95) and gliotic events were detected by glial fibrillary acidic protein (GFAP).
HNPCs were not able to inhibit photoreceptor cell death in co-cultured retinal explants. However, the progenitor cells had the ability to preserve synaptic integrity to some extent, as observed by maintained PSD95 immunoreactivity in photoreceptor cell terminals. Retinal co-cultures also showed reduced GFAP expression in Müller cells which was interpreted as decreased gliosis. Milliplexed HNPCs medium showed that several neuroprotective factors were secreted, including FGF-2, G-CSF, GM-CSF and VEGF.
Our observations indicate that, although HNPC derived factors did not have the capacity to protect photoreceptors from cell death after three days of co-culture, maintenance of synaptic integrity and decreased gliosis appeared to be favored.
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