Synthesis of 3D magnetic porous carbon derived from a metal-organic framework for the extraction of clenbuterol and ractopamine from mutton samples.

3D magnetic porous carbon (MPCK) was prepared using the metal-organic framework (MOF) MIL-100(Fe) as the carbon precursor by carbonisation and KOH activation strategies. Carbonisation and activation ensured that MPCK possessed excellent structural and thermal stability, strong magnetic responsiveness and high surface area. MPCK was used as an adsorbent for the magnetic solid-phase extraction of clenbuterol and ractopamine from mutton samples. The concentration levels of analytes were determined by ultra-high performance liquid chromatography-mass spectrometry. Under optimised extraction conditions, the peak area responded linearly to analytes over the concentration range from 0.05 µg L-1 to 40 µg L-1 (r ≥ 0.9972). The detection limits of clenbuterol and ractopamine were found to be 0.130 µg kg-1 and 0.150 µg kg-1, respectively. The satisfactory recoveries in mutton samples ranging from 95.64% to 114.65% indicated that 3D porous carbon is a promising adsorption material for the extraction of clenbuterol and ractopamine from complex biological matrixes.

Pressure-stabilized polymerization of nitrogen in alkaline-earth-metal strontium nitrides.

High-pressure technology can help us to obtain excellent materials. We have explored alkaline-earth-metal strontium nitrides under different pressures, theoretically. A variety of stable Sr-N structures were predicted by the structure searching method using CALYPSO code. Six new stoichiometries, SrN, Sr2N3, SrN2, SrN3, SrN4, and SrN5, were predicted. And our calculation proved that all these compounds were stable existing under ambient pressure up to 100 GPa. A rich variety of poly-nitrogen forms appeared in the newly predicted SrNx compounds, including four nitrogen polymerization forms: ranging from N2, N3, N4, and N5 molecules, to zig-zag nitrogen chains and extended chains connected by puckered "N6" rings. Significantly, the 1D extended polymeric chain of puckered "N6" rings was firstly identified in the P1[combining macron]-SrN3 structure at 60 GPa. Another N-rich C2/c-SrN4 was stable only under the relatively high-pressure of 20 GPa, but this phase can be quenched under atmospheric pressure. The N-rich phase SrN5 maintained structural stability when the pressure reached 50-70 GPa. The delocalization of π electrons from N atoms was the principal cause for its metallicity in SrN5. In this paper, our calculated results indicated that the energetic poly-nitrides in alkaline-earth-metal nitrides can be obtained by the high-pressure method.

Fabrication of glucose-derived carbon-decorated magnetic microspheres for extraction of bisphenols from water and tea drinks.

Glucose-derived carbon-decorated magnetic microspheres were synthesized by an easy hydrothermal carbonization method and used as a high-efficiency adsorbent to extract bisphenols in water and tea drinks. The as-prepared carbon-decorated magnetic microspheres had a well-defined core-shell structure with a shell thickness of about 5 nm. The microspheres possessed high saturation magnetization at 60.8 emu/g and excellent chemical stability in aqueous solution. The experimental parameters affecting the extraction efficiency, including extraction time, pH, adsorbent dosage, desorption solvents, desorption time, and solution volume were evaluated. Electrostatic and π-π interactions were the major driving forces during extraction. Overall, a new magnetic solid-phase extraction method of determining bisphenols was developed on the basis of as-prepared magnetic microspheres. The method had a wide linear range, low limits of detection (0.03-0.10 µg/L), and high recoveries (85.4-104.6%).

Analysis of microcystins using high-performance liquid chromatography and magnetic solid-phase extraction with silica-coated magnetite with cetylpyridinium chloride.

Microcystins (MCs), produced by freshwater cyanobacteria, can be serious water pollutants, so it is important to monitor their concentration in drinking water. We have developed a method for rapid and accurate determination of microcystin levels in environmental water, using magnetic solid-phase extraction and high-performance liquid chromatography with UV detection. The magnetic composite material, which was combined with cetylpyridinium chloride, was prepared by hydrothermal synthesis. The optimal extraction of microcystins in water sample was achieved by optimizing the amount of adsorbent, time of adsorption, ratio of eluting solvent, and volume of eluent. Under the optimal conditions, the limit of detection of MC-LR was 0.001 µg/L, and the limit of quantification was 0.0028 µg/L. The limit of detection of MC-RR was 0.001 µg/L, and the limit of quantification was 0.003 µg/L. These values are far lower than those established by the International Health Organization for the maximum concentration of microcystins in drinking water. The magnetic solid-phase extraction adsorbent used in this method has the advantages of simple preparation, low price, and easy solid-liquid separation, and it can be used for the rapid and sensitive monitoring of trace microcystins in environmental water samples.

Preparation and application of a coated-fiber needle extraction device.

In this study, a needle-trap device with fibers coated with a molecularly imprinted polymer was developed for separation. A number of heat-resistant Zylon filaments were longitudinally packed into a glass capillary, followed by coating with a molecularly imprinted polymer. Then, the molecularly imprinted polymer coating was copolymerized and anchored onto the surface of the fibers. The bundle of synthetic fibers coated with the molecularly imprinted polymer was packed into a 21G stainless-steel needle and served as an extraction medium. The coated-fiber needle extraction device was used to extract volatile organic compounds from paints and gasoline effectively. Subsequently, the extracted volatile organic compounds were analyzed by gas chromatography. Calibration curves of gaseous benzene, toluene, ethylbenzene, and o-xylene in the concentration range of 1-250 µg/L were obtained to evaluate the method, acceptable linearity was attended with correlation coefficients above 0.998. The limit of detection of benzene, toluene, ethylbenzene, and o-xylene was 11-20 ng/L using the coated-fiber needle-trap device. The relative standard deviation of needle-to-needle repeatability was less than 8% with an extraction time of 20 min. The loss rates after storage for 3 and 7 days at room temperature were less than 30%.

ZIF-67-modified magnetic nanoparticles for extraction of phenoxy carboxylic acid herbicides.

Phenoxy carboxylic acid (PCA) herbicides are commonly used herbicides that can easily accumulate in soil, groundwater, crops, and vegetable surfaces. Thus, they pose a serious risk to human health. Accurate detection of trace amounts of PCAs in various matrixes is crucial. Herein, ZIF-67-modified magnetic nanoparticles (MNPs, ZIF-67@Fe3O4) were prepared by growing ZIF-67 on the surface of Fe3O4 MNPs. The introduction of ZIF-67 improved the dispersion of Fe3O4 nanoparticles in water and enhanced their extraction performance for PCAs. When an eluent consisting of ammonia water and acetonitrile (5% : 95%; v/v) was employed, 10 mg of ZIF-67@Fe3O4 displayed optimal extraction performance for PCAs in a 20 mL sample solution at a pH of 3. We achieved a limit of detection ranging from 0.014 µg L-1 to 0.056 µg L-1 for four types of PCA herbicides by using the newly developed method. Notably, the values were considerably lower than the maximum concentration levels of PCAs in drinking water set by the Environmental Protection Agency. The relative recovery rate of PCAs using ZIF-67@Fe3O4 ranged from 83.75% to 117.07% when applied to river water and apple samples. These results demonstrate the great potential of ZIF-67@Fe3O4 in determining the residues of organic pesticides in real samples.

SIRT1 Inhibits High Glucose-Induced TXNIP/NLRP3 Inflammasome Activation and Cataract Formation.

Purpose: To determine whether SIRT1 regulates high glucose (HG)-induced inflammation and cataract formation through modulating TXNIP/NLRP3 inflammasome activation in human lens epithelial cells (HLECs) and rat lenses. Methods: HG stress from 25 to 150 mM was imposed on HLECs, with treatments using small interfering RNAs (siRNAs) targeting NLRP3, TXNIP, and SIRT1, as well as a lentiviral vector (LV) for SIRT1. Rat lenses were cultivated with HG media, with or without the addition of NLRP3 inhibitor MCC950 or SIRT1 agonist SRT1720. High mannitol groups were applied as the osmotic controls. Real-time PCR, Western blots, and immunofluorescent staining evaluated the mRNA and protein levels of SIRT1, TXNIP, NLRP3, ASC, and IL-1ß. Reactive oxygen species (ROS) generation, cell viability, and death were also assessed. Results: HG stress induced a decline in SIRT1 expression and caused TXNIP/NLRP3 inflammasome activation in a concentration-dependent manner in HLECs, which was not observed in the high mannitol-treated groups. Knocking down NLRP3 or TXNIP inhibited NLRP3 inflammasome-induced IL-1ß p17 secretion under HG stress. Transfections of si-SIRT1 and LV-SIRT1 exerted inverse effects on NLRP3 inflammasome activation, suggesting that SIRT1 acts as an upstream regulator of TXNIP/NLRP3 activity. HG stress induced lens opacity and cataract formation in cultivated rat lenses, which was prevented by MCC950 or SRT1720 treatment, with concomitant reductions in ROS production and TXNIP/NLRP3/IL-1ß expression levels. Conclusions: The TXNIP/NLRP3 inflammasome pathway promotes HG-induced inflammation and HLEC pyroptosis, which is negatively regulated by SIRT1. This suggests viable strategies for treating diabetic cataract.

Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model.

Purpose: Dry eye disease (DED) is a multifactorial disease that is associated with inflammation. Excessive DNA is present in the tear fluid of patients with DED. Absent in melanoma 2 (AIM2) is a key DNA sensor. This study aimed to investigate the role of AIM2 in the pathogenesis of DED. Methods: DED was induced by injection of scopolamine (SCOP). Aberrant DNA was detected by cell-free DNA (cfDNA) ELISA and immunostaining. Corneal epithelial defects were assessed by corneal fluorescein staining, zonula occludens-1 immunostaining and TUNEL. Tear production was analyzed by phenol red thread test. Lacrimal gland (LG) histology was evaluated by hematoxylin and eosin staining, and transmission electron microscopy examination. Macrophage infiltration in LG was detected by immunohistochemistry for the macrophage marker F4/80. Gene expression was analyzed by RT-qPCR. Protein production was examined by immunoblot analysis or ELISA. Results: Aim2-/- mice displayed a normal structure and function of LG and cornea under normal conditions. In SCOP-induced DED, wild type (WT) mice showed increased cfDNA in tear fluid, and aberrant accumulations of dsDNA accompanied by increased AIM2 expression in the LG. In SCOP-induced DED, WT mice displayed damaged structures of LG, reduced tear production, and severe corneal epithelium defects, whereas Aim2-/- mice had a better preserved LG structure, less decreased tear production, and improved clinical signs of dry eye. Furthermore, genetic deletion of Aim2 suppressed the increased infiltration of macrophages and inhibited N-GSDMD and IL18 production in the LG of SCOP-induced DED. Conclusions: Aim2 deficiency alleviates ocular surface damage and LG inflammation in SCOP-induced DED.

Fluorescence Imaging of Diabetic Cataract-Associated Lipid Droplets in Living Cells and Patient-Derived Tissues.

Diabetic cataract (DC) surgery carries risks such as slow wound healing, macular edema, and progression of retinopathy and is faced with a deficiency of effective drugs. In this context, we proposed a protocol to evaluate the drug's efficacy using lipid droplets (LDs) as the marker. For this purpose, a fluorescent probe PTZ-LD for LDs detection is developed based on the phenothiazine unit. The probe displays polarity-dependent emission variations, i.e., lower polarity leading to stronger intensity. Especially, the probe exhibits photostability superior to that of Nile Red, a commercial LDs staining dye. Using the probe, the formation of LDs in DC-modeled human lens epithelial (HLE) cells is validated, and the interplay of LDs-LDs and LDs-others are investigated. Unexpectedly, lipid transfer between LDs is visualized. Moreover, the therapeutic efficacy of various drugs in DC-modeled HLE cells is assessed. Ultimately, more LDs were found in lens epithelial tissues from DC patients than in cataract tissues for the first time. We anticipate that this work can attract more attention to the important roles of LDs during DC progression.

A molecular beacon-like Ag nanocluster fluorescence probe for nucleic acid detection.

We have developed a type of low-cost, label-free silver nanocluster molecular beacon-like fluorescence sensor with a DNA template. To detect target DNA with this probe, we use a hairpin DNA sequence based on a "turn-on" strategy. The transformation of hairpin DNA would visibly influence the formation of Ag nanoclusters, such that the stronger fluorescence will be measured with the solution containing target nucleic acids than that without targets nucleic acids. There is a good liner relationship between the fluorescence and the target DNA concentrations, ranging from 1 to 750 nmol L-1. Importantly, the detection sensing platform allows down to 1 nmol L-1, which is much lower than other studies.

Velvet-like carbon nitride as a solid-phase microextraction fiber coating for determination of polycyclic aromatic hydrocarbons by gas chromatography.

In this study, velvet-like carbon nitride (V-g-C3N4) was prepared from urea aqueous solutions by one-step thermal polycondensation. The V-g-C3N4 material was then characterized using a scanning electron microscope (SEM), X-ray diffractometer (XRD), Fourier transform infrared spectrophotometer (FT-IR), and nitrogen adsorption-desorption isotherms. The specific surface area of V-g-C3N4 (60.66 m2/g) was 1.8 times that of the carbon nitride (g-C3N4) prepared by the traditional method. V-g-C3N4 was modified on the surface of stainless-steel wire by a sol-gel technique to obtain a solid-phase microextraction (SPME) coating for the extraction of five polycyclic aromatic hydrocarbons (PAHs) from water samples. The chromatography signal of the PAHs extracted using the V-g-C3N4 coating was 1.5 times that when using a g-C3N4 coating, and 5-10 times that when using commercial PDMS. Under the optimized extraction conditions, the linear range of the method developed for the determination of five PAHs was 0.05-100 µg/L, the limits of detection were 0.005-0.012 µg/L, and the recoveries from actual water samples were 85.94-103.47%. Furthermore, the developed SPME device is remarkably durable and can be reused up to 160 times.

Coating layered double hydroxides with carbon dots for highly efficient removal of multiple dyes.

Layered double hydroxides (LDHs) and layered double oxides (LDOs) are desirable adsorption materials for printing and wastewater treatment owing to their outstanding anion exchange abilities, abundant active sites, and eco-friendly nature. In this study, a versatile LDO hybrid coated with carbon dots (CDs@MgAl-LDO) was constructed by modifying sodium dodecylbenzene sulfonate on the surface of MgAl-LDH as a carbon precursor, followed by ligand carbonization and hydrotalcite dehydration at 450 °C under N2 flow. CDs@MgAl-LDO displayed a hexagonal lamellar architecture with a plate lateral size of approximately 500 nm. It had a higher BET specific surface area (28.61 m2/g) than MgAl-LDO (11.48 m2/g). X-ray diffraction analysis revealed that CDs@MgAl-LDO maintained the "memory effect" of LDOs and could retrieve the original structure when dispersed in water. Moreover, the modified carbon dots change the intrinsically hydrophilic nature of LDOs and help to improve the affinity for organic contaminants, including both cationic and anionic dyes. The adsorption of dyes on CDs@MgAl-LDO followed a pseudo-second-order kinetic model with correlation coefficients (R2) ranging from 0.9901 to 0.9911 and exhibited Freundlich-type heterogeneous adsorption. It showed superior adsorption performance for three dyes, with the maximum adsorption capacity of 3628.9-5174.1 mg/g, thereby outperforming previously reported LDH-based adsorbents. This work developed a facile approach for preparing new carbon dots-LDH hybrids for the highly efficient removal of multiple dyes.

Magnetic porous carbons derived from iron-based metal-organic framework loaded with glucose for effective extraction of synthetic organic dyes in drinks.

The conversion of metal-organic frameworks (MOFs) to porous carbon has attracted extensive attention for developing multifunctional adsorbent materials. Herein, we demonstrated a facile method to prepare magnetic porous carbon via calcinating MIL-101(Fe) precursor loaded with glucose at 700 °C in an N2 atmosphere. The obtained magnetic porous carbon (MPCG) contained plenty of oxygen-containing functional groups and exhibited an enlarged specific surface area (177.7 m2/g) compared with its precursor (41.2 m2/g). In addition, MPCG can be easily separated from the matrix by a magnet. Benefitting from these advantages, the magnetic porous carbon exhibited high affinity toward four synthetic organic dyes (amaranth, ponceau 4R, sunset yellow, and lemon yellow) in an aqueous solution. Moreover, the adsorbent can be applied to quantitatively detect synthetic organic dyes in drinks coupled with chromatography. A new magnetic solid-phase extraction method for dye analysis yielded reasonable linearity (r â–¡ 0.99), low limits of detection (0.047-0.076 µg/L), and good precision within the analyte concentration range of 0.25-50 µg/L.

Observation of HOCl generation associated with diabetic cataract using a highly sensitive fluorescent probe.

Diagnosis of diabetic cataract (DC) in the early stage is of great significance for drug intervention and surgery circumvention for DC patients. However, the lack of reliable imaging tools greatly limits the diagnosis of early DC. In this context, a fluorescent probe BBPy for hypochlorous acid (HOCl) is presented based on the oxidation of phenothiazine. The probe displays apparent emission enhancement at 562 nm toward HOCl with high selectivity, superb sensitivity (detection limit: 12.6 nM), and rapid response (within seconds). Using the probe, the HOCl generation in diabetic human lens epithelial cells was monitored, as well as the HOCl down-regulation during antioxidant treatment. Therefore, it is proposed that HOCl can be a promising biomarker for DC and fluorescence imaging technique can be regarded as a candidate tool for DC diagnosis.

Sensitivity of the Dorsal-Central Retinal Pigment Epithelium to Sodium Iodate-Induced Damage Is Associated With Overlying M-Cone Photoreceptors in Mice.

Purpose: Retinal pigment epithelium (RPE) degeneration is a leading cause of blindness in retinal degenerative diseases, but the mechanism of RPE regional degeneration remains largely unknown. This study aims to investigate the sensitivity of RPE to sodium iodate (SI) injury in the dorsal and ventral visual fields in mice and analyze whether overlaying cone photoreceptors regulate the sensitivity of RPE to SI-induced damage. Methods: SI was used to induce RPE degeneration in mice. Hematoxylin-eosin staining, immunostaining, and TUNEL assay were used to evaluate retinal degeneration along the dorsal-ventral axis. Flat-mounted and sectional retinal immunostaining were used to analyze the distribution of cones along the dorsoventral axis in C57BL/6, albino, and 129 mice. Electroretinography was used to examine the retinal function. Results: Dorsal-central RPE was more sensitive to SI-mediated injury along the dorsal-ventral axis in C57BL/6 mice. Compared with the ventral RPE, the dorsal-central RPE was dominantly covered by M cone photoreceptors in these mice. Interestingly, M cone photoreceptor degeneration was followed by dorsal RPE degeneration under a low dose of SI. Furthermore, the sensitivity of dorsal RPE to a low dose of SI was reduced in both albino and 129 mouse strains with dominant mixed cones instead of M cones in the dorsal visual field. Conclusions: These findings suggest that dorsal-central RPE is more sensitive to SI injury and that SI-induced RPE degeneration could be controlled by modifying the dominant overlying cone population in the mouse dorsal retina, thereby highlighting a potential role of M cones in RPE regional degeneration.

High dose expression of heme oxigenase-1 induces retinal degeneration through ER stress-related DDIT3.

BACKGROUND: Oxidative stress is a common cause of neurodegeneration and plays a central role in retinal degenerative diseases. Heme oxygenase-1 (HMOX1) is a redox-regulated enzyme that is induced in neurodegenerative diseases and acts against oxidative stress but can also promote cell death, a phenomenon that is still unexplained in molecular terms. Here, we test whether HMOX1 has opposing effects during retinal degeneration and investigate the molecular mechanisms behind its pro-apoptotic role. METHODS: Basal and induced levels of HMOX1 in retinas are examined during light-induced retinal degeneration in mice. Light damage-independent HMOX1 induction at two different expression levels is achieved by intraocular injection of different doses of an adeno-associated virus vector expressing HMOX1. Activation of Müller glial cells, retinal morphology and photoreceptor cell death are examined using hematoxylin-eosin staining, TUNEL assays, immunostaining and retinal function are evaluated with electroretinograms. Downstream gene expression of HMOX1 is analyzed by RNA-seq, qPCR examination and western blotting. The role of one of these genes, the pro-apoptotic DNA damage inducible transcript 3 (Ddit3), is analyzed in a line of knockout mice. RESULTS: Light-induced retinal degeneration leads to photoreceptor degeneration and concomitant HMOX1 induction. HMOX1 expression at low levels before light exposure prevents photoreceptor degeneration but expression at high levels directly induces photoreceptor degeneration even without light stress. Photoreceptor degeneration following high level expression of HMOX1 is associated with a mislocalization of rhodopsin in photoreceptors and an increase in the expression of DDIT3. Genetic deletion of Ddit3 in knockout mice prevents photoreceptor cell degeneration normally resulting from high level HMOX1 expression. CONCLUSION: The results reveal that the expression levels determine whether HMOX1 is protective or deleterious in the retina. Furthermore, in contrast to the protective low dose of HMOX1, the deleterious high dose is associated with induction of DDIT3 and endoplasmic reticulum stress as manifested, for instance, in rhodopsin mislocalization. Hence, future applications of HMOX1 or its regulated targets in gene therapy approaches should carefully consider expression levels in order to avoid potentially devastating effects.

High-pressure formation of antimony nitrides: a first-principles study.

The structural phase transition, electronic properties, and bonding properties of antimony nitrides have been studied by using the first principles projector augmented wave method. The relationship between the formation enthalpy and the composition of the Sb-N system has been explored. The novel Sb2N3 with the Cmcm space group is stable in a narrow pressure range from 100 GPa to 120 GPa. Apart from the Sb2N3, two nitrogen-rich phases SbN2 and SbN4 were predicted. The SbN2 with the C2/m space group is stable at 12 GPa and then transforms to the high-pressure phase at 23 GPa. The nitrogen-rich SbN4 appears at 14 GPa then undergoes C2/m → P1̄ → P1̄ phase transitions, and the calculated pressures of the phase transitions are 31 and 60 GPa, respectively. The nitrogen-rich SbN2 and SbN4 have similar structural features. Both SbN2 and SbN4 can be seen as a sandwich structure composed of the Sb-N layers and N2 dimers. The pressure-induced phase transitions of SbN2 and SbN4 are accompanied by the electron transfer between the Sb-N layers and N2 dimers. Moreover, the nitrogen-rich SbN4 has a higher energy density of 2.42 kJ g-1 and is a potentially high energy density material.

[Analysis of fatty acids in rice by pseudotargeted metabolomics method based on gas chromatography-mass spectrometry].

A pseudotargeted metabolomics method based on gas chromatography-mass spectrometry (GC-MS) was developed for the analysis of fatty acids in rice. A total of 16 fatty acids were detected in rice. The method was used to identify the difference between fatty acid profiles in rice. The total intensity of the saturated and unsaturated fatty acids was used as the evaluation index. The effects of six extraction methods and four extraction solvents on the extraction efficiencies of the fatty acids were compared. The developed method was used to investigate the fatty acid profiles in five types of rice (Daohuaxiang, Jixing, Jinlangzi, Nongda, and Zhuangyuan). The fatty acid profile in Daohuaxiang rice was different from that in the other four species. The fatty acids in Jinlangzi and Nongda rice were markedly different, while those in Jixing and Jinlangzi rice were similar. The method is simple, stable and accurate, and it can provide basic data for the improvement of rice quality and nutritional value.

Dispersive solid-phase extraction of bisphenols migrated from plastic food packaging materials with cetyltrimethylammonium bromide-intercalated zinc oxide.

The migration of bisphenols (BPs) can take place from plastic packaging materials into freshly cooked takeaway food, especially at high temperatures. In this study, cetyltrimethylammonium bromide-intercalated zinc oxide (ZnO@CTAB) was developed and used to extract the migration of BPs (bisphenol A and bisphenol AF) from disposable plastic materials to contained food simulates. Several experimental parameters that influence extraction efficiency were investigated. Under optimal conditions, a sensitive dispersive solid-phase extraction method based on ZnO@CTAB was proposed for the analysis of BPs coupled with ultra-high performance liquid chromatography and time-of-flight mass spectrometry. The method exhibited good linearity of calibration, high recovery (97.63-109.33%), low limits of detection 0.027-0.030 µg L-1, and acceptable precisions. The developed method was used to carry out a migration test from two disposable plastic bags and a disposable plastic container, using distilled water at 100 °C as a hot liquid food simulant. The migration concentrations of bisphenol AF was found to be 0.42 µg L-1 and 0.86 µg L-1 for the two types of disposable plastic bags, and the concentration of bisphenol A was 0.49 µg L-1 for disposable plastic container. The proposed method was also applied to investigate the migration of BPAF from the disposable plastic bags to different food simulants, revealing that the release of BPAF levels depended on the polarity of the liquid food components.

KIT ligand protects against both light-induced and genetic photoreceptor degeneration.

Photoreceptor degeneration is a major cause of blindness and a considerable health burden during aging but effective therapeutic or preventive strategies have not so far become readily available. Here, we show in mouse models that signaling through the tyrosine kinase receptor KIT protects photoreceptor cells against both light-induced and inherited retinal degeneration. Upon light damage, photoreceptor cells upregulate Kit ligand (KITL) and activate KIT signaling, which in turn induces nuclear accumulation of the transcription factor NRF2 and stimulates the expression of the antioxidant gene Hmox1. Conversely, a viable Kit mutation promotes light-induced photoreceptor damage, which is reversed by experimental expression of Hmox1. Furthermore, overexpression of KITL from a viral AAV8 vector prevents photoreceptor cell death and partially restores retinal function after light damage or in genetic models of human retinitis pigmentosa. Hence, application of KITL may provide a novel therapeutic avenue for prevention or treatment of retinal degenerative diseases.