ABSTRACT
The eye is closely connected to the brain, providing a unique window to detect pathological changes in the brain. In this study, we discovered ß-amyloid (Aß) deposits along the ocular glymphatic system in patients with Alzheimer's disease (AD) and 5×FAD transgenic mouse model. Interestingly, Aß from the brain can flow into the eyes along the optic nerve through cerebrospinal fluid (CSF), causing retinal degeneration. Aß is mainly observed in the optic nerve sheath, the neural axon, and the perivascular space, which might represent the critical steps of the Aß transportation from the brain to the eyes. Aquaporin-4 facilitates the influx of Aß in brain-eye transport and out-excretion of the retina, and its absence or loss of polarity exacerbates brain-derived Aß induced damage and visual impairment. These results revealed brain-to-eye Aß transport as a major contributor to AD retinopathy, highlighting a new therapeutic avenue in ocular and neurodegenerative disease.
Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Aquaporin 4 , Brain , Glymphatic System , Mice, Transgenic , Retinal Degeneration , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Animals , Amyloid beta-Peptides/metabolism , Humans , Retinal Degeneration/metabolism , Retinal Degeneration/pathology , Brain/metabolism , Brain/pathology , Mice , Aquaporin 4/metabolism , Aquaporin 4/genetics , Glymphatic System/metabolism , Glymphatic System/pathology , Retina/metabolism , Retina/pathology , Optic Nerve/metabolism , Optic Nerve/pathology , Male , Female , Disease Models, Animal , Mice, Inbred C57BL , AgedABSTRACT
The demand for terahertz (THz) communication and detection fuels continuous research for high performance of THz absorption materials. In addition to varying the materials and their structure passively, an alternative approach is to modulate a THz wave actively by tuning an external stimulus. Correlated oxides are ideal materials for this because the effects of a small external control parameter can be amplified by inner electronic correlations. Here, by utilizing an unpatterned strongly correlated electron oxide VO2 thin film, a photoinduced broad-band tunable THz absorber is realized first. The absorption, transmission, reflection, and phase of THz waves can all be actively controlled by an external pump laser above room temperature. By varying the laser fluence, the average broad-band absorption can be tuned from 18.9 to 74.7% and the average transmission can be tuned from 9.2 to 69.2%. Meanwhile, a broad-band antireflection is obtained at 5.6 mJ/cm2, and a π-phase shift of a reflected THz wave is achieved when the fluence increases greater than 5.7 mJ/cm2. Apart from other modulators, the photoexcitation-assisted dual-phase competition is identified as the origin of this active THz multifunctional modulation. Our work suggests that advantages of controllable phase separation in strongly correlated electron systems could provide viable routes in the creation of active optical components for THz waves.