Microcebus murinus retina: A new model to assess prion-related neurotoxicity in primates

Abstract

No effective treatment currently exists for prion diseases and therefore the development of experimental non-human primate models of prion neurotoxicity, to better understand the underlying mechanism and to test new treatments relevant to humans, represents an urgent medical need. However, the establishment of such models is challenging due to animal welfare and cost considerations. We describe here the use of Microcebus murinus retina, in primary cultures and in vivo, as a new experimental primate model to rapidly examine the effects in the central nervous system of PrP106–126, a neurotoxic fragment of the human prion protein. We demonstrate that PrP106–126 triggered rod photoreceptor cell loss by apoptosis and a change in morphology of microglial cells in mixed neuronal–glial cultures of retinal cells. In addition, 2 days after intravitreal injection of PrP106–126, retinas showed a significant increase in the number of apoptotic nuclei, mainly in the ganglion cell layer.

Keywords

• Prion
• Amyloid fibril
• Neurotoxicity
• Primate