BACKGROUND: The pathogenesis of Alzheimer's disease (AD) is characterized by neuronal injury, activation of microglia and astrocytes, deposition of amyloid-β and secondary vessel degeneration. In the polycystic kidney disease (PKD) rat model, we observed neuronal injury, microglial activation and vasoregression. We speculated that this neuroretinal degeneration shares important pathogenetic steps with AD. Therefore, we determined the activation of astrocytes and the accumulation of amyloid-β in PKD retinae. METHODS: Immunohistochemistry of PKD retinae for vimentin, carboxymethyllysin, beta-Amyloid 1-42, High-Mobility-Group- Protein B1 and amyloid protein precursor was performed. RESULTS: Adjunct to astrocyte activation, accumulation of beta-Amyloid 1-42 and High-Mobility-Group-Protein B1 in astrocytes and around vessels of the superficial network was found in PKD retinae prior to the onset of vasoregression. Amyloid precursor protein was localized adjacent to the outer segment of photoreceptors in PKD and control rats. The parallel appearance of AD-related peptides indicates an alarmine based response to photoreceptor degeneration and secondary vasoregression. CONCLUSION: The model has broad overlap with AD and may be suitable to study beneficial pharmacological concepts.
BACKGROUND: The pathogenesis of Alzheimer's disease (AD) is characterized by neuronal injury, activation of microglia and astrocytes, deposition of amyloid-β and secondary vessel degeneration. In the polycystic kidney disease (PKD) rat model, we observed neuronal injury, microglial activation and vasoregression. We speculated that this neuroretinal degeneration shares important pathogenetic steps with AD. Therefore, we determined the activation of astrocytes and the accumulation of amyloid-β in PKD retinae. METHODS: Immunohistochemistry of PKD retinae for vimentin, carboxymethyllysin, beta-Amyloid 1-42, High-Mobility-Group- Protein B1 and amyloid protein precursor was performed. RESULTS: Adjunct to astrocyte activation, accumulation of beta-Amyloid 1-42 and High-Mobility-Group-Protein B1 in astrocytes and around vessels of the superficial network was found in PKD retinae prior to the onset of vasoregression. Amyloid precursor protein was localized adjacent to the outer segment of photoreceptors in PKD and control rats. The parallel appearance of AD-related peptides indicates an alarmine based response to photoreceptor degeneration and secondary vasoregression. CONCLUSION: The model has broad overlap with AD and may be suitable to study beneficial pharmacological concepts.
Authors: Gunjan D Manocha; Atreyi Ghatak; Kendra L Puig; Susan D Kraner; Christopher M Norris; Colin K Combs Journal: J Alzheimers Dis Date: 2017 Impact factor: 4.472
Authors: Juan M Zolezzi; Sussy Bastías-Candia; Manuel J Santos; Nibaldo C Inestrosa Journal: Front Aging Neurosci Date: 2014-07-28 Impact factor: 5.750