Retinal hypoxia triggers abnormal vessel growth and microvascular hyper‐permeability in ischemic retinopathies. Whereas vascular endothelial growth factor A (VEGF‐A) inhibitors significantly hinder disease progression, their benefits to retinal neurons remain poorly understood. Similar to humans, oxygen‐induced retinopathy (OIR) mice exhibit severe retinal microvascular malformations and profound neuronal dysfunction. OIR mice are thus a phenocopy of human retinopathy of prematurity, and a proxy for investigating advanced stages of proliferative diabetic retinopathy. Hence, the OIR model offers an excellent platform for assessing morpho‐functional responses of the ischemic retina to anti‐angiogenic therapies. Using this model, we investigated the retinal responses to VEGF‐Trap (Aflibercept), an anti‐angiogenic agent recognizing ligands of VEGF receptors 1 and 2 that possesses regulatory approval for the treatment of neovascular age‐related macular degeneration, macular edema secondary to retinal vein occlusion and diabetic macular edema. Our results indicate that Aflibercept not only reduces the severity of retinal microvascular aberrations but also significantly improves neuroretinal function. Aflibercept administration significantly enhanced light‐responsiveness, as revealed by electroretinographic examinations, and led to increased numbers of dopaminergic amacrine cells. Additionally, retinal transcriptional profiling revealed the concerted regulation of both angiogenic and neuronal targets, including transcripts encoding subunits of transmitter receptors relevant to amacrine cell function. Thus, Aflibercept represents a promising therapeutic alternative for the treatment of further progressive ischemic retinal neurovasculopathies beyond the set of disease conditions for which it has regulatory approval.
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We investigate the temporal and spectral properties of subpicosecond pulses transmitted on the heavy-hole exciton transition through a multiple-quantum-well Bragg structure, exhibiting a one-dimensional photonic band gap. At low light intensities, a temporal propagation beating is observed. This beating is strongly dependent on the optical dephasing time T 2 which is dominated by the radiative interwell coupling. In an intermediate intensity regime, the Pauli-blocking nonlinearity leads to gradual suppression of the photonic band gap and vanishing of the linear propagation beating. For highly nonlinear excitation, we find signatures of selfinduced transmission due to Rabi flopping and adiabatic following of the carrier density. Numerical simulations using the semiconductor Maxwell-Bloch equations are in excellent agreement with the experimental data up to intensities for which higher many-particle correlations become more important and self-phase modulation occurs in the sample substrate.
We demonstrate that the temporal pulse phase remains essentially unaltered before separate phase characteristics are developed when propagating high-intensity pulses coherently on the exciton resonance of an optically thick semiconductor. This behavior is a clear manifestation of self-induced transmission and pulse breakup into soliton-like pulses due to Rabi flopping of the carrier density. Experiments using a novel fast-scan cross-correlation frequency-resolved optical gating (XFROG) method are in good agreement with numerical calculations based on the semiconductor Bloch equations.
The adiabatic driving of the resonant electron dynamics in a one-dimensional resonant photonic band gap is proposed as an optical mechanism for nonlinear ultrafast switching. Pulsed excitation inside the photonic gap results in an ultrafast suppression and recovery of the gap. This behavior results from the adiabatic carrier dynamics due to rapid radiative damping inside the band gap.The time scale of the optical response in nano-optical systems near resonance is limited by the response time of the structured material and the duration of the excitation pulse. If all intrinsic relaxation processes in the material are fast compared to the duration of the excitation pulse, the optical pulse adiabatically drives the material variables and determines their temporal response. 1 In this Paper, we theoretically analyze and quantitatively explain this principle for pulse shaping and optical switching in a half-wavelength (i.e., spacing /2) periodic semiconductor structure, recently observed experimentally in Ref. 2. The analysis of the nonlinear reflection experiments 2 in pump-probe geometry, is carried out on the basis of the coupled semiconductor Maxwell-Bloch equations, recently used to explain the transmission of short single pulses through multiple quantum well Bragg structures. 3 In multiple quantum well structures (MQW), with spacing great enough to eliminate direct Coulomb interaction between the quantum wells (QWs), the excitonic resonances inside the different QWs couple radiatively. 4-6 If the QWs are in Bragg periodicity, a super-radiant mode develops leading to a broad resonant photonic band gap 3,7-13 which for a large number of QWs results in the band gap of a onedimensional photonic crystal. 14,15 Long-lived and short-lived polariton modes in such Bragg (and anti-Bragg) structures have been discussed. 16 Also the influence of defects in MQW photonic crystals and their optical properties have been studied. 17 Typical bandwidths are on the order of 10-20 meV, compared to 1-2 meV for the spectral width of a switching pulse. The resonant band gap itself is similar to a passive dielectric band gap of a Bragg reflector caused by multiple reflection at the periodic surfaces and interference effects (analytic solutions are known from atomic systems 18 ). However, in contrast to passive dielectrics, the excitonic resonance which forms the band gap, can be directly influenced by the strength of the light field because of strong optical nonlinearities due to Coulomb many body and other interaction effects, and Pauli blocking. Such nonlinearities may lead to exciton saturation resulting in a breakdown of the band gap. 19 In this Paper, we show that a strong laser pulse propagates-besides reflection-without strong reshaping if its spectrum is completely inside the optical band gap. This pulse suppresses the photonic band gap for the time of its duration, thus allowing for a femtosecond switching mechanism. This behavior is caused by Pauli blocking and Coulomb nonlinearities of the carrier density which adiabatically f...
Dedicated to Professor Dr. Roland Zimmermann on the occasion of his 60th birthdayThe occurrence of non-Lorentzian lineshapes is analyzed for a variety of nanooptical semiconductor systems such as quantum wells and quantum dots. Their origin is traced back to light-matter interaction (light propagation) and many-particle correlations (electron-electron and electronphonon interaction).
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