Primary open angle glaucoma (POAG) is a neurodegenerative disease characterized by physiological intraocular hypertension that causes damage to the retinal ganglion cells (RGCs). In the past, RGC damage in POAG was suggested to have been attributed to RGC apoptosis. However, in the present study, we applied a model closer to human POAG through the use of a chronic hypertensive glaucoma model in rhesus monkeys to investigate whether another mode of progressive cell death, autophagy, was activated in the glaucomatous retinas. First, in the glaucomatous retinas, the levels of LC3B-II, LC3B-II/LC3B-I and Beclin 1 increased as demonstrated by Western blot analyses, whereas early or initial autophagic vacuoles (AVi) and late or degraded autophagic vacuoles (AVd) accumulated in the ganglion cell layer (GCL) and in the inner plexiform layer (IPL) as determined by transmission electron microscopy (TEM) analysis. Second, lysosome activity and autophagosome-lysosomal fusion increased in the RGCs of the glaucomatous retinas, as demonstrated by Western blotting against lysosome associated membrane protein-1 (LAMP1) and double labeling against LC3B and LAMP1. Third, apoptosis was activated in the glaucomatous eyes with increased levels of caspase-3 and cleaved caspase-3 and an increased number of TUNEL-positive RGCs. Our results suggested that autophagy was activated in RGCs in the chronic hypertensive glaucoma model of rhesus monkeys and that autophagy may have potential as a new target for intervention in glaucoma treatment.
For the first time to our knowledge, these data collectively establish the existence of hallmark AD-like pathologies in the glaucomatous LGN. Our results may provide new targets for developing research therapies that will enhance neuroprotection in glaucoma patients.
A d15 mode piezoelectric energy harvester (PEH) with two PZT-51 elements in series connection (SC), in which the elements are arranged along the width direction, was fabricated, and it is compared with the traditional d15 mode PEH with a single PZT-51 element (SPEH) to discuss the output peak-to-peak voltage (Up−p). The energy harvesting performances of PEHSC are modeled by combining the single degree of freedom model and the electrical model with the piezoelectric constitutive equation of the d15 mode. The energy harvesting performances of PEHSC were systematically measured at various frequencies and load resistances, and Up−p and output power are 12.4 V and 8.7 μW at a load resistance of 2.2 MΩ and resonance frequency of 73 Hz. The experimental Up−p of PEHSC and SPEH are 25.4 and 15.6 V at the resonance frequencies under open circuit condition, and this indicates that the SC structure can improve the energy harvesting performance for d15 mode PEH. The experimental Up−p, output power and the transient voltage–time curve of PEHSC are in agreement with the results of finite element numerical solutions and theoretical modeling, so they are acceptable. The d15 mode and SC structure could potentially improve the energy harvesting performance of PEHs.
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