Progranulin Deficiency Causes TDP43 Mislocalization and Neuron Death in the Retina

Neurodegeneration and cytoplasmic mislocalization of TDP43 are pathologic hallmarks of sporadic frontotemporal lobar dementia TDP-43 subtype (FTLD-TDP) and familial FTLD caused by GRN mutations. However, the relationship between progranulin (PGRN)-deficiency, TDP43 mislocalization, and neuronal death remains unclear. Though brains from PGRN-deficient mice display some pathologic features of FTLD, neither a robust neurodegenerative phenotype nor TDP43 redistribution occurs. As such, fundamental aspects of FTLD pathogenesis have been difficult to model in these mice. Because retinal abnormalities are early feature of other neurodegenerative diseases, suggesting that retinal neurons are an especially vulnerable cell population in the CNS, we investigated whether retinal pathology occurred in a mouse model of GRN-deficient FTLD.