Herein, we show the ability to control nonlinear optical nanocrystal orientation and nanostructure orientation at the same time in the Li2O-Nb2O5-SiO2 glass by high repetition rate (100-500 kHz) femtosecond laser direct writing. A self-rganized nanostructure with nanoscale phase separation, nonlinear optical nanocrystals embedded in an amorphous network, can be oriented by laser polarization. With the increase of laser power, three modified regimes are revealed. At low laser power, a modified amorphous structure is obtained and has higher HF etching rate than that of the glass substrate. At moderate laser power, polar axes of nanocrystals tend to be perpendicular to laser polarization direction. The range of pulse energy narrows dramatically with the increase of repetition rate. At high laser power, microcrystals are obtained and crystallization is very sensitive to writing mode (the angle between writing direction and laser polarization direction). These findings shed light on the comprehension of ultra-fast laser-matter interaction and provide a new path toward fabricating three-dimensional optical devices.

During ultrafast laser-induced crystallization from glass with a non-congruent composition, a phase separation occurs. The morphology of the crystallized area, inside the heat-affected zone (HAZ), is spectacular showing a bouquet-like structure, under some specific conditions related to glass chemical composition and laser parameters. In this work, we investigate this HAZ along a written line through a set of high-resolution electron microscopy techniques to probe both the morphology and the chemical distribution at the nanoscale. Based on these findings, we demonstrate that the bouquet-like structure arises from poorly textured nanocrystals between two regions that have probably accumulated elastic strain. From that analysis, we also provide insights into the chemical separation process during this complex light-matter transformation in which the induced plasma structure guides the spatial distribution of SiO2 and LiNbO3. We suggest a model based on an electric field modulation produced by the inhomogeneous plasma electron trapping, that modifies the electrochemical potentials of the constituents.

Hierarchical micro/nanostructure surface structures with different spatial characteristics are achieved after irradiation of crystalline silicon via femtosecond (fs) laser pulses (800 nm, 120 fs, 1 kHz) with the sample submerged in ethanol. According to laser pulse energy and fabrication parameters (such as scanning speed and superimposed writing), a characteristic morphology evolution of ovoid-like smooth modified area, ripple-like, wave-like, and coral-like micro/nanostructures is demonstrated, and the underline principle is discussed. The amorphization of fs laser-modified area is verified and investigated by Raman spectroscope. These modified structures have potential applications in sensors, silicon photovoltaic cells, and sterilization.

Exudative age-related macular degeneration (AMD), characterized by choroidal neovascularization (CNV), is the leading cause of irreversible blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) drugs are the standard treatment for AMD, but they have limitations. Cell therapy is a promising approach for ocular diseases, and it is being developed in the clinic for the treatment of retinal degeneration, including AMD. We previously showed that subretinal injection of human umbilical tissue-derived cells (hUTCs) in a rodent model of retinal degeneration preserved photoreceptors and visual function through rescue of retinal pigment epithelial (RPE) cell phagocytosis. Here we investigated the effect of hUTCs on a rat model of laser-induced CNV and on a human RPE cell line, ARPE-19, for VEGF production. We demonstrate that subretinal injection of hUTCs significantly inhibited CNV and lowered choroidal VEGF in vivo. VEGF release from ARPE-19 decreased when co-cultured with hUTCs. Soluble VEGF receptor 1 (sVEGFR1) is identified as the only factor in hUTC conditioned medium (CM) that binds to VEGF. The level of exogenous re-combinant VEGF in hUTC CM was dramatically reduced and could be recovered with sVEGFR1-neutralizing antibody. This suggests that hUTC inhibits angiogenesis through the secretion of sVEGFR1 and could serve as a novel treatment for angiogenic ocular diseases, including AMD.

Laser-induced crystallization in glasses is of great interest because of its significant applications in optics. However, the mechanisms involved are not yet concluded, and this paper is aimed at making progress on this problem. Major aspects of laser-induced crystallization are the nanostructure formation, textured crystallization, and growth dynamics. Lithium niobium silicate glasses were used as a "glass model" to investigate the nanostructure formation and crystallization by femtosecond (fs) laser irradiation at a high repetition rate (100-500 kHz). Three crystallization regimes can be classified with the increase of laser power. In addition, the boundary between neighboring regimes can be adjusted by changing the writing parameters. Regime 1: modifications of the amorphous structure. Regime 2: appearance of textured nanocrystals embedded in amorphous lamellas. Polar axes of nanocrystals are perpendicular to laser polarization direction. Remarkably, this hierarchical micro-/nanostructure can induce an orientation tunable second harmonic generation and form birefringence. Regime 3: crystallization morphology is sensitive to the angle between laser writing and laser polarization direction. With parallel configuration, crystal grains are at the micron scale. With perpendicular configuration, crystal morphologies resemble regime 2, but they are not textured. A crystallization dynamic model is proposed to explain the various nano-/microcrystals formation and their morphology induced by fs laser irradiation. This model allows thinking that it is possible to extend conclusions to other noncongruent glasses. This provides guidelines for manufacturing multifunctional optical devices.

Femtosecond laser-induced refractive index changes in lithium niobium silicate glass were explored at high repetition rate (300 fs, 500 kHz) by polarized light microscopy, full-wave retardation plate, quantitative birefringence microscopy, and digital holographic microscopy. We found three regimes on energy increase. The first one corresponds to isotropic negative refractive index change (for pulse energy ranging 0.4-0.8 μJ/pulse, 0.6 NA, 5μm/s, 650μm focusing depth in the glass). The second one (0.8-1.2 μJ/pulse) corresponds to birefringence with well-defined slow axis orientation. The third one (above 1.2 μJ/pulse) is related to birefringence direction fluctuation. Interestingly, these regimes are consistent with crystallization ones. In addition, an asymmetric orientational writing effect has been detected on birefringence. These topics extend the possibility of controlling refractive index change in multi-component glasses.

Background Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly characterized by retinal pigment epithelium (RPE) degeneration with accumulation of abnormal intracellular deposits (lipofuscin) and photoreceptor death. RPE is vital for the retina and integrity of photoreceptors through its phagocytic function which is closely linked to formation of lipofuscin through daily phagocytosis of discarded photoreceptor outer segments (POS). Although phagocytosis has been implicated in AMD, it has not been directly shown to be altered in AMD. RPE phagocytic defect was previously shown to be rescued by subretinal injection of human umbilical tissue derived cells (hUTC) in a rodent model of retinal degeneration (RCS rat) through receptor tyrosine kinase (RTK) ligands and bridge molecules. Here, we examined RPE phagocytic function directly in the RPE from AMD patients and the ability and mechanisms of hUTC to affect phagocytosis in the human RPE. Methods Human RPE was isolated from the post-mortem eyes of normal and AMD-affected subjects and cultured. RPE phagocytic function was measured in vitro using isolated POS. The effects of hUTC conditioned media, recombinant RTK ligands brain-derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and glial cell-derived neurotrophic factor (GDNF), as well as bridge molecules milk-fat-globule-EGF-factor 8 (MFG-E8), thrombospondin (TSP)-1, and TSP-2 on phagocytosis were also examined in phagocytosis assays using isolated POS. RNA was isolated from normal and AMD RPE treated with hUTC conditioned media and subjected to transcriptome profiling by RNA-Seq and computational analyses. Results RPE phagocytosis, while showing a moderate decline with age, was significantly reduced in AMD RPE, more than expected for age. hUTC conditioned media stimulated phagocytosis in the normal human RPE and significantly rescued the phagocytic dysfunction in the AMD RPE. RTK ligands and bridge molecules duplicated the rescue effect. Moreover, multiple molecular pathways involving phagocytosis, apoptosis, oxidative stress, inflammation, immune activation, and cholesterol transport were affected by hUTC in the RPE. Conclusions We demonstrated for the first time RPE phagocytic dysfunction in AMD, highlighting its likely importance in AMD, and the ability of hUTC to correct this dysfunction, providing insights into the therapeutic potential of hUTC for AMD.

Understanding the phase transformation in glass and the morphology of related nanostructure after femtosecond laser irradiation is of great importance for fabricating functional optics, in which glass crystallization is involved to obtain nonlinear optical properties. We report on the crystallization inside lithium niobium silicate glass induced by fs laser irradiation. Energy‐dispersive X‐ray spectroscopy coupled to scanning transmission electron microscopy (STEM/EDS) and transmission electron microscopy confirm a nanoscale phase separation whereby LiNbO3 crystals are embedded in lamella‐shaped frames of amorphous SiO2. The obtained nanostructure may have applications in fabricating second‐order nonlinear optical devices.

We explore the femtosecond laser-induced modifications (i.e., morphology, crystallization, and nanostructure) in Li <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O-Nb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> -SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> glass at high-repetition-rate (1030nm, 300fs, 300 kHz) to get insight on the ultrafast laser-matter interaction according to pulse energy and writing configuration. Three-dimensional SHG patterns with controllable angular dependence were achieved. Electron backscatter diffraction indicated that the angular dependence was associated to preferential nanocrystals orientation: crystal polar axes are distributed within a plane perpendicular to the incident laser polarization direction.

We explore femtosecond laser-induced modifications (i.e., morphology, crystallization, and nanostructure) in lithium niobium silicate glass at high repetition rates (1030 nm, 300 fs, and 300 kHz) to get insight on the ultrafast laser-matter interaction according to the pulse energy and writing configuration (the laser polarization direction versus scanning one). The modifications can be classified into three regimes according to pulse energy: (1) at 0.3-0.4 mu J/pulse, one amorphous zone with a larger sensitivity to chemical etching; (2) at 0.5-0.9 mu J/pulse, textured nanocrystals embedded in lamella-like amorphous phases whatever the laser polarization or scanning direction is; and (3) at 1.0-2.2 mu J/pulse, crystallization dependent on the writing configuration. Remarkably, we show in this paper that the orientation of the nanostructure can be controlled by laser polarization. In addition, this nanostructure is investigated in three dimensions by a combination of scanning electron microscope, electron backscatter diffraction, and transmission electron microscopy. This finding may guide users to the optimal parameters for applications in optics. (C) 2016 Optical Society of America

Summary form only given. Self-organized nanostructures including nonlinear crystals (i.e. LiNbOs) are obtained inside lithium niobium silicate glass via femtosecond (fs) laser irradiation (1030 nm, 300 fs) in a single-step processing.As shown in Fig. 1, scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD) are used to characterize the specificities of such nanostructures. It was found that nanostructure including LiNbO3 can be obtained in Zone D (i.e. the centre of laser-modified area in Fig.1a). As illustrated in Fig. 1b-e, two types of organizations are pointed out: one is along the laser propagation direction (i.e. Z direction) and the other one is along laser polarization direction (i.e. Y direction). Moreover, at certain laser pulse energy, textured nano-crystals are obtained embedded in lamella-like amorphous phases, investigated by transmission electron microscopy and EBSD [1-3].

Mastering second-harmonic generation (SHG) in glasses is essential for achieving second-order nonlinear devices. Three-dimensional SHG patterns with controllable angular dependence were achieved in Li2O-Nb2O5-SiO2 glass by femtosecond laser irradiation. Electron backscatter diffraction indicated that the angular dependence was associated with preferential nanocrystal orientation: crystal polar axes are distributed within a plane perpendicular to the incident laser polarization direction. An orientation mechanism based on the application of laser-induced torques on the nanocrystal electric dipole was proposed. This work may pave the way to design devices such as frequency agile lasers based on electro-optical waveguides. (C) 2016 Optical Society of America

We demonstrate a new kind of form birefringence in lithium niobium silicate glass induced by femtosecond laser direct writing. By combining electron backscatter diffraction and transmission electron microscopy, we reveal a self-assembled nanostructure consisting of periodic phase change: nonlinear optical nanocrystals embedded in a network of "walls" in a vitreous phase. These "walls" are aligned perpendicular to the laser polarization direction. This self-organized nanostructure may successfully explain the origin of the laser-induced birefringence in this multicomponent glass quite differently from pure silica. These findings highlight a spectacular modification of glass, and enable construction of a high contrast three-dimensional refractive index and birefringent structures at the micrometer scale in multicomponent glasses.

To control second harmonic generation (SHG) in silica-based glasses is crucial for fabricating photonic devices, such as frequency doubling waveguides. Here, we investigated SHG of laser induced nonlinear optical crystals in silica-based glasses, according to writing speed and pulse energy. We observed two regions with different probing laser polarization angular dependence: a) a well-defined cosine-like curve with period of 180° at low pulse energy (0.8 μJ) whatever the writing speed or at high pulse energy (1.4 μJ) with high writing speed (25 μm/s). This is accounted for by a well-defined texture for the nano crystals with their polar axis oriented perpendicular to the writing laser polarization; and b) a double cosine-like curve revealing a second texture of the crystals at high pulse energy (1.4 μJ) with low writing speed (5 μm/s) and with the polar axis oriented closer parallel to the writing laser polarization. Therefore, a SHG dependence on probing laser polarization angle may show high contrast by a correct choice of the writing speed and pulse energy. These results pave the way for elaboration of nonlinear optical devices.

Retinal pigment epithelium (RPE) cells perform many functions crucial for retinal preservation and vision. RPE cell dysfunction results in various retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD). Currently, there are no effective treatments for retinal degeneration except for a small percentage of individuals with exudative AMD. Cell therapies targeting RPE cells are being developed in the clinic for the treatment of retinal degeneration. Subretinal injection of human umbilical tissue-derived cells (hUTC) in the Royal College of Surgeons (RCS) rat model of retinal degeneration was shown to preserve photoreceptors and visual function. However, the precise mechanism remains unclear. Here, we demonstrate that hUTC rescue phagocytic dysfunction in RCS RPE cells in vitro. hUTC secrete receptor tyrosine kinase (RTK) ligands brain-derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and glial cell-derived neurotrophic factor (GDNF), as well as opsonizing bridge molecules milk-fat-globule-epidermal growth factor 8 (MFG-E8), growth arrest-specific 6 (Gas6), thrombospondin (TSP)-1, and TSP-2. The effect of hUTC on phagocytosis rescue in vitro is mimicked by recombinant human proteins of these factors and is abolished by siRNA-targeted gene silencing in hUTC. The bridge molecules secreted from hUTC bind to the photoreceptor outer segments and facilitate their ingestion by the RPE. This study elucidates novel cellular mechanisms for the repair of RPE function in retinal degeneration through RTK ligands and bridge molecules, and demonstrates the potential of using hUTC for the treatment of retinal degenerative diseases.