Deficiency of SECTM1 impairs corneal wound healing in aging.

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re-epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non-human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.

Fabrication of bioengineered corneal endothelial grafts using an allogeneic cornea-derived matrix.

Corneal endothelial keratoplasty has been the primary treatment method of endothelial decompensation, but it is often limited in clinical practice due to global shortage of donor cornea. Here, we explored using an ultra-thin allogeneic cornea-derived matrix (uACM) films as a substrate for constructing bioengineered corneal endothelial grafts. We evaluated the films' optical, mechanical, and structural properties, and measured the composition of the extracellular matrix. The uACM was an ultrathin and curved cornea-shaped film with favorable optical and mechanical properties. The fabrication process efficiently preserved corneal extracellular matrix composition and significantly decreased cellular components. Moreover, human corneal endothelial cells and rabbit corneal endothelial cells (RCECs) can adhere and grow on the uACM films with a positive expression of the corneal endothelial functional markers Na+/K+-ATPase and ZO-1. The successful transplantation of uACM with RCECs grafts into the rabbit model of endothelial dysfunction via Descemet membrane endothelial keratoplasty resulted in prompt restoration of corneal transparency and thickness. During the four-week follow-up period, the uACM with RCECs implanted eyes exhibited comparable corneal transparency, central corneal thickness, and endothelial cell count to that of the healthy rabbit. Histologic examination revealed that the grafts were successfully attached and integrated onto the posterior surface of the corneal stroma. The uACM achieved biomimetic reconstruction in terms of both composition and structure, and can be used to construct the bioengineered corneal endothelial grafts. These results indicate that constructing bioengineered corneal endothelial grafts from discarded human corneal tissues may pave the way for generating high-quality corneal endothelial grafts for transplantation.

The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation.

Proper differentiation of corneal epithelial cells (CECs) from limbal stem/progenitor cells (LSCs) is required for maintenance of ocular homeostasis and clear vision. Here, using a single-cell transcriptomic atlas, we delineate the comprehensive and refined molecular regulatory dynamics during human CEC development and differentiation. We find that RORA is a CEC-specific molecular switch that initiates and drives LSCs to differentiate into mature CECs by activating PITX1. RORA dictates CEC differentiation by establishing CEC-specific enhancers and chromatin interactions between CEC gene promoters and distal regulatory elements. Conversely, RORA silences LSC-specific promoters and disrupts promoter-anchored chromatin loops to turn off LSC genes. Collectively, our work provides detailed and comprehensive insights into the transcriptional dynamics and RORA-mediated epigenetic remodeling underlying human corneal epithelial differentiation.

Single-cell transcriptomics implicates the FEZ1-DKK1 axis in the regulation of corneal epithelial cell proliferation and senescence.

Limbal stem/progenitor cells (LSC) represent the source of corneal epithelium renewal. LSC proliferation and differentiation are essential for corneal homeostasis, however, the regulatory mechanism remains largely unexplored. Here, we performed single-cell RNA sequencing and discovered proliferation heterogeneity as well as spontaneously differentiated and senescent cell subgroups in multiply passaged primary LSC. Fasciculation and elongation protein zeta 1 (FEZ1) and Dickkopf-1 (DKK1) were identified as two significant regulators of LSC proliferation and senescence. These two factors were mainly expressed in undifferentiated corneal epithelial cells (CECs). Knocking down the expression of either FEZ1 or DKK1 reduced cell division and caused cell cycle arrest. We observed that DKK1 acted as a downstream target of FEZ1 in LSC and that exogenous DKK1 protein partially prevented growth arrest and senescence upon FEZ1 suppression in vitro. In a mouse model of corneal injury, DKK1 also rescued the corneal epithelium after recovery was inhibited by FEZ1 suppression. Hence, the FEZ1-DKK1 axis was required for CEC proliferation and the juvenile state and can potentially be targeted as a therapeutic strategy for promoting recovery after corneal injury.

ETS1-HMGA2 Axis Promotes Human Limbal Epithelial Stem Cell Proliferation.

Purpose: This study aimed to investigate the role and molecular mechanism of ETS1 in the proliferation and differentiation of human limbal epithelial stem cells (LESCs). Methods: RNA-seq and quantitative real-time PCR were used to determine gene expression changes when ETS1 and HMGA2 was knocked down using short-hairpin RNAs or overexpressed by lentivirus. Immunofluorescence and flow cytometry experiments were performed to assess the roles of ETS1 and HMGA2 in LESC proliferation. ETS1-bound cis-regulatory elements and target genes in LESCs were identified using chromatin immunoprecipitation sequencing. The epigenetic features of ETS1-binding sites were assessed by the published histone modification and chromatin accessibility profiles. Results: ETS1 was robustly expressed in LESCs but dramatically reduced on differentiation into corneal epithelial cells (CECs). ETS1 knockdown in LESCs inhibited cellular proliferation and activated CEC markers (KRT3, KRT12, CLU, and ALDH3A1). When ETS1 was overexpressed during CEC differentiation, LESC-associated genes were upregulated while CEC-associated genes were downregulated. The genome-wide binding profile of ETS1 was identified in LESCs. ETS1 occupied H3K4me3-marked promoters and H3K27ac/H3K4me1-marked enhancers. ETS1-binding sites were also enriched for chromatin accessibility signal. HMGA2 showed a consistent expression pattern with ETS1. ETS1 activates HMAG2 by binding to its promoter. Knockdown and overexpression experiments suggested that HMGA2 can promote LESC proliferation and inhibits its differentiation. Conclusions: ETS1 promotes LESC proliferation and inhibits its differentiation via activating HMGA2.

Amniotic Membrane Enhances the Characteristics and Function of Stem Cell-Derived Retinal Pigment Epithelium Sheets by Inhibiting the Epithelial-Mesenchymal Transition.

Human pluripotent stem cell-derived retinal pigment epithelium (iRPE) is an attractive cell source for disease modeling and cell replacement therapy of retinal disorders with RPE defects. However, there are still challenges to develop appropriate culture conditions close to in vivo microenvironment to generate iRPE sheets, which mimic more faithfully the characteristics and functions of the human RPE cells. Here, we developed a simple, novel platform to construct authentic iRPE sheets using human amniotic membrane (hAM) as a natural scaffold. The decellularized hAM (dAM) provided a Bruch's membrane (BM)-like bioscaffold, supported the iRPE growth and enhanced the epithelial features, polarity distribution and functional features of iRPE cells. Importantly, RNA-seq analysis was performed to compare the transcriptomes of iRPE cells cultured on different substrates, which revealed the potential mechanism that dAM supported and promoted iRPE growth was the inhibition of epithelial-mesenchymal transition (EMT). The tissue-engineered iRPE sheets survived and kept monolayer when transplanted into the subretinal space of rabbits. All together, our results indicate that the dAM imitating the natural BM allows for engineering authentic human RPE sheets, which will provide valuable biomaterials for disease modeling, drug screening and cell replacement therapy of retinal degenerative diseases. STATEMENT OF SIGNIFICANCE: Engineered RPE sheets have a great advantage over RPE cell suspension for transplantation as they support RPE growth in an intact monolayer which RPE functions are dependent on. The substrates for RPE culture play a critical role to maintain the physiological functions of the RPE in stem cell therapies for patients with retinal degeneration. In this study, we constructed engineered iRPE sheets on the decellularized human amniotic membrane scaffolds, which contributed to enhancing epithelial features, polarity distribution and functional features of iRPE. dAM exhibited the ability of anti-epithelial mesenchymal transition to support iRPE growth. Furthermore, the results of transplantation in vivo demonstrated the feasibility of iRPE sheets in retina regenerative therapy. Engineering RPE sheets on dAM is a promising strategy to facilitate the development of iRPE replacement therapy and retinal disease modeling.

Comprehensive 3D epigenomic maps define limbal stem/progenitor cell function and identity.

The insights into how genome topology couples with epigenetic states to govern the function and identity of the corneal epithelium are poorly understood. Here, we generate a high-resolution Hi-C interaction map of human limbal stem/progenitor cells (LSCs) and show that chromatin multi-hierarchical organisation is coupled to gene expression. By integrating Hi-C, epigenome and transcriptome data, we characterize the comprehensive 3D epigenomic landscapes of LSCs. We find that super-silencers mediate gene repression associated with corneal development, differentiation and disease via chromatin looping and/or proximity. Super-enhancer (SE) interaction analysis identified a set of SE interactive hubs that contribute to LSC-specific gene activation. These active and inactive element-anchored loop networks occur within the cohesin-occupied CTCF-CTCF loops. We further reveal a coordinated regulatory network of core transcription factors based on SE-promoter interactions. Our results provide detailed insights into the genome organization principle for epigenetic regulation of gene expression in stratified epithelia.

dsRNA Induced IFNß-MMP13 Axis Drives Corneal Wound Healing.

Purpose: Cornea, the outermost transparent layer of the eye, is the first line of defense against external threats. Following injury, the wound healing response is crucial to corneal repair and regeneration, yet its underlying mechanism is poorly understood. Our study was designed to investigate the role of dsRNA and its regulatory network in corneal wound healing. Methods: A corneal wound healing model was established via the surgical removal of half of the corneal surface and adjoining limbus. RNase III was then used to clarify the role of dsRNA in corneal wound closure and RNA-seq was performed to investigate the mechanism of dsRNA in the healing process. Related gene expression was assessed using immunofluorescence staining, qPCR, and Western blot. Flow cytometry and scratch assay were used to analyze the proliferation and migration of limbal stem/progenitor cells (LSCs) in vitro and functional analysis of the target genes was completed using the corneal wound healing model. Results: Corneal wound healing was delayed and impaired when the dsRNAs were removed or damaged following RNase III digestion. The dsRNAs released following corneal damage activate type I interferon (IFN-I) signaling, primarily IFNß, via the corneal epithelium and neutralizing IFNß or blocking IFN-I signaling delays corneal wound closure. Moreover, our data identified MMP13 as a downstream effector of IFNß where its expression promotes LSC proliferation and enhances corneal epithelial reconstruction in vivo. Conclusions: The dsRNA induced IFNß-MMP13 axis plays a key role in corneal wound healing.

Occurrence of Oxidative Stress and Premature Senescence in the Anterior Segment of Acute Primary Angle-Closure Eyes.

Purpose: To explore whether oxidative stress and premature senescence occur in the anterior segment of acute primary angle-closure (APAC) eyes after increased intraocular pressure. Methods: The eye samples of 21 APAC patients, 22 age-related cataract patients, and 10 healthy donors were included. Aqueous humor (AqH), iris, and anterior lens capsule samples were collected. The levels of oxidative stress markers and senescence-associated secretory phenotype (SASP)-related cytokines in AqH were estimated using relevant reagent kits and multiplex bead immunoassay technique. The intensity of relevant markers in anterior segment tissues was examined by immunofluorescence- and senescence-associated ß-galactosidase (SA-ß-gal) staining. Results: Oxidative stress marker levels elevated significantly in the AqH of APAC eyes. Reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine levels were positively correlated with preoperative peak intraocular pressure and age, whereas reduced glutathione/oxidized glutathione (GSH/GSSH) ratio was negatively correlated with both parameters. The levels of several SASP-related cytokines were markedly increased. ROS and malondialdehyde levels were positively correlated with the levels of some SASP-related cytokines, whereas superoxide dismutase level and GSH/GSSH ratio showed an opposite trend. The number of cells positive for oxidative mitochondrial DNA damage and apoptosis-related markers increased in the iris and anterior lens capsule of the APAC group. Senescence-associated markers (p16, p21, and p53) and SA-ß-gal activity were increased in the iris of the APAC group. Conclusions: Oxidative stress and premature senescence occurred in the anterior segment of APAC patients, suggesting that they may be involved in the development of pathological changes in the anterior segment of APAC eyes.

Construction of bioengineered corneal stromal implants using an allogeneic cornea-derived matrix.

The bioengineering of corneal scaffolds that mimic native human cornea has attracted interest owing to the scarcity of donor corneas for the transplantation-based treatment of corneal blindness. However, an optimally engineered corneal tissue for clinical use has yet to emerge. Herein, human corneal tissues discarded during allogeneic corneal transplantation surgery were used to construct allogeneic cornea-derived matrix (ACM) scaffolds with favorable optical properties and structural strength. During scaffold fabrication, collagen and glycosaminoglycan levels were well preserved, while DNA decreased significantly. Scanning electron microscopy revealed the presence of fiber-like structures on the scaffold surface and specific structures featuring multiple interlaced lamellae in cross-sections. Moreover, corneal epithelial cells grown on the ACM formed a continuous multi-stratified epithelium with a strong expression of the corneal epithelial differentiation marker CK3/12, gap junction marker Connexin43, and stem-cell-specific marker p63α, while corneal stromal cells expressed the keratocyte-specific marker KERA and the adhesion marker integrin ß1. When the ACM was implanted into rabbit corneal stromal pockets, the rabbit cornea remained transparent throughout the follow-up period. These results indicate that the construction of corneal stromal implants from discarded human corneal tissues may pave the way for the generation of high-quality corneal tissue for transplantation.

Comparison of Descemet Membrane Endothelial Keratoplasty for Iridocorneal Endothelial Syndrome and Fuchs Endothelial Dystrophy.

PURPOSE: To evaluate the clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) for treating eyes with iridocorneal endothelial (ICE) syndrome and comparing the outcomes with those achieved after treating Fuchs endothelial dystrophy (FED). DESIGN: Prospective interventional comparative case series. METHODS: Sixty-three patients (68 eyes) with ICE syndrome or FED were enrolled at the Zhongshan Ophthalmic Center between March 10, 2014 and May 11, 2018. Eligible patients were divided into 2 groups: ICE group (eyes, 24; patients, 24) and FED group (eyes, 44; patients, 39). DMEK was performed in all cases. Corrected distance visual acuity (CDVA), endothelial cell loss (ECL), intraocular pressure (IOP), graft survival, and surgical complications were documented. RESULTS: In the ICE and FED groups, the mean follow-up duration was 24.9 ± 5 months and 25.2 ± 7.7 months, respectively. At 1 year postoperatively, Kaplan-Meier survival analysis demonstrated 85.7% and 100% cumulative graft success rates (P = .017) in patients with ICE and FED, respectively. Postoperative CDVA level was comparable between the 2 groups through 12-month follow-up; thereafter CDVA was better in the FED group than in the ICE group (P < .001). Moreover, postoperative ECL was significantly higher in the ICE group than in the FED group throughout the follow-up period (P < .001). A discernable increase in structural abnormalities of the anterior chamber angle was observed in 2 eyes (8.3%) in the ICE group; however, no significant differences were observed in the incidence of principal complications between the 2 groups. CONCLUSIONS: DMEK provides comparable short-term visual outcomes in the treatment of ICE to those observed in the treatment of FED, with higher postoperative ECL over FED.

Descemet membrane endothelial keratoplasty for corneal decompensation caused by a phakic anterior chamber intraocular lens implantation.

PURPOSE: To describe the clinical outcomes of Descemet membrane endothelial keratoplasty combined with phacoemulsification/posterior chamber intraocular lens implantation (triple procedure) for treatment of corneal decompensation induced by a phakic anterior chamber intraocular lens (AC IOL) implantation. METHODS: Ten patients (10 eyes) with corneal decompensation due to phakic AC IOL implantation that had undergone the triple procedure were included in this study. Among the 10 eyes, 5 eyes underwent explantation of AC IOL prior to the transplantation, and then underwent the triple procedure. The remaining 5 eyes with a phakic AC IOL in situ underwent the triple procedure with concurrent explantation of AC IOL. Corrected distance visual acuity (CDVA), subjective refraction, endothelial cell density (ECD), and complications were documented. RESULTS: The triple procedure was performed across all eyes without any adverse events. The average CDVA improved from 1.32 ± 0.24 preoperatively to 0.15 ± 0.05 logarithm of the minimum angle of resolution (logMAR), which represents an improvement in Snellen equivalent from 20/400 (0.05) preoperatively to 20/28 (0.71) at 12 months after surgery. At 12 months, all eyes reached a CDVA of 20/32 (0.63) or better, and 50% of eyes reached a CDVA of 20/25 (0.8) or better. The mean donor ECD±SD was 2868.7 ± 67.9 cells/mm2, which decreased to 1724.1 ± 84.6 cells/mm2 at 12 months, representing 39.9% of endothelial cell loss. Patients did not experience any severe adverse events. CONCLUSION: The triple procedure is a safe and effective option for corneal decompensation induced by a phakic AC IOL implantation, helping achieve a satisfactory visual rehabilitation with few complications.

AICAR prolongs corneal allograft survival via the AMPK-mTOR signaling pathway in mice.

Immune rejection is a critical complication that results in the graft failure after corneal transplantation. Thus, there remains a need for new therapies for allograft rejection. AICAR (aminoimidazole-4-carboxamide ribonucleoside) is an, as adenosine monophosphate-activated protein kinase (AMPK) activator and a purine nucleoside with a wide range of metabolic effects, including activation of AMPK. More recently, it was reported that it is possible to inhibiting organs rejection and prolong the graft survival time in various models of organ transplantation. In this study, we systematically evaluated the efficacy of AICAR as a treatment modality for inhibiting allograft rejection in a mouse model of corneal transplantation. We found that AICAR significantly suppressed the opacity, edema, and vascularization of the graft, resulting in prolonged corneal allograft survival. AICAR treatment also significantly decreased central corneal thickness. Moreover, the AICAR-treated group showed decreased expression of IB4 and VEGF as compared to the control group. In addition, the mRNA expression of T helper 1 cytokines (IL-2, INF-γ, and TNF-α) was suppressed, and the expression of T helper 2 cytokines (IL-4, IL-5, and IL-13) was elevated by AICAR. Furthermore, the western blotting results revealed that AICAR stimulated AMPK activation and inhibited angiogenesis and inflammation possibly by subsequently suppressing mTOR phosphorylation. By contrast, the AMPK inhibitor Compound C (also called dorsomorphin) had the opposite effect. Our results showed that Compound C blocked AMPK-mTOR signaling and promoted the angiogenesis and inflammation, thus compromising the graft survival. These results suggest that AICAR may be a potential option for inhibiting the corneal graft rejection and for prolonging the graft survival.

Boosting Two-Dimensional MoS2/CsPbBr3 Photodetectors via Enhanced Light Absorbance and Interfacial Carrier Separation.

Transition metal dichalcogenides (TMDs) are promising candidates for flexible optoelectronic devices because of their special structures and excellent properties, but the low optical absorption of the ultrathin layers greatly limits the generation of photocarriers and restricts the performance. Here, we integrate all-inorganic perovskite CsPbBr3 nanosheets with MoS2 atomic layers and take the advantage of the large absorption coefficient and high quantum efficiency of the perovskites, to achieve excellent performance of the TMD-based photodetectors. Significantly, the interfacial charge transfer from the CsPbBr3 to the MoS2 layer has been evidenced by the observed photoluminescence quenching and shortened decay time of the hybrid MoS2/CsPbBr3. Resultantly, such a hybrid MoS2/CsPbBr3 photodetector exhibits a high photoresponsivity of 4.4 A/W, an external quantum efficiency of 302%, and a detectivity of 2.5 × 1010 Jones because of the high efficient photoexcited carrier separation at the interface of MoS2 and CsPbBr3. The photoresponsivity of this hybrid device presents an improvement of 3 orders of magnitude compared with that of a MoS2 device without CsPbBr3. The response time of the device is also shortened from 65.2 to 0.72 ms after coupling with MoS2 layers. The combination of the all-inorganic perovskite layer with high photon absorption and the carrier transport TMD layer may pave the way for novel high-performance optoelectronic devices.

Enhancing Optoelectronic Properties of Low-Dimensional Halide Perovskite via Ultrasonic-Assisted Template Refinement.

Low-dimensional halide perovskite (HP) has triggered lots of research attention in recent years due to anisotropic optoelectronic/semiconducting properties and enhanced stability. High-quality low-dimensional HPs via controllable engineering are required to fulfill the encouraging promise for device applications. Here, we introduce, for the first time, postsynthetic ultrasonic-assisted refinement of two-dimensional homologous HPs (OA2PbBr4, OA is octadecylamine). The solution-prepared OA2PbBr4, either in the form of large-sized microcrystal or nanosheet, obtains significantly enhanced crystallinity after ultrasonic treatment. We further show that OA2PbBr4 nanosheets can be used as a template to construct low-dimensional CsPbBr3 with the size and morphology inherited. Importantly, we found the ultrasonic-treated OA2PbBr4 crystals, compared with pristine ones, lead to enhanced optoelectronic properties for the resultant low-dimensional CsPbBr3, as demonstrated by improved photodetection performances, including prolonged charge-carrier lifetime, improved photostability, increased external quantum yield/responsivity, and faster response speed. We believe this work provides novel engineering of low-dimensional HPs beyond the reach of straightforward synthesis.

Antimonene Oxides: Emerging Tunable Direct Bandgap Semiconductor and Novel Topological Insulator.

Highly stable antimonene, as the cousin of phosphorene from group-VA, has opened up exciting realms in the two-dimensional (2D) materials family. However, pristine antimonene is an indirect band gap semiconductor, which greatly restricts its applications for optoelectronics devices. Identifying suitable materials, both responsive to incident photons and efficient for carrier transfer, is urgently needed for ultrathin devices. Herein, by means of first-principles computations we found that it is rather feasible to realize a new class of 2D materials with a direct bandgap and high carrier mobility, namely antimonene oxides with different content of oxygen. Moreover, these tunable direct bandgaps cover a wide range from 0 to 2.28 eV, which are crucial for solar cell and photodetector applications. Especially, the antimonene oxide (18Sb-18O) is a 2D topological insulator with a sizable global bandgap of 177 meV, which has a nontrivial Z2 topological invariant in the bulk and the topological states on the edge. Our findings not only introduce new vitality into 2D group-VA materials family and enrich available candidate materials in this field but also highlight the potential of these 2D semiconductors as appealing ultrathin materials for future flexible electronics and optoelectronics devices.

Low-Voltage Photodetectors with High Responsivity Based on Solution-Processed Micrometer-Scale All-Inorganic Perovskite Nanoplatelets.

All-inorganic photodetectors based on scattered CsPbBr3 nanoplatelets with lateral dimension as large as 10 µm are fabricated, and the CsPbBr3 nanoplatelets are solution processed governed by a newly developed ion-exchange soldering mechanism. Under illumination of a 442 nm laser, the photoresponsivity of photodetectors based on these scattered CsPbBr3 nanoplatelets is as high as 34 A W-1 , which is the largest value reported from all-inorganic perovskite photodetectors with an external driven voltage as small as 1.5 V. Moreover, the rise and fall times are 0.6 and 0.9 ms, respectively, which are comparable to most of the state-of-the-art all-inorganic perovskite-based photodetectors. All the material synthesis and device characterization are conducted at room temperature in ambient air. This work demonstrates that the solution-processed large CsPbBr3 nanoplatelets are attractive candidates to be applied in low-voltage, low-cost, ultra highly integrated optoelectronic devices.

Constructing Fast Carrier Tracks into Flexible Perovskite Photodetectors To Greatly Improve Responsivity.

Intrinsically high mobility and large absorption coefficient endow inorganic halide perovskites (IHPs) with great promise for high-performance photodetectors (PDs), which, however, are being hindered by the low carrier extraction and transport efficiency of the solution assembled films. Here, we report on a general strategy to enhance the perovskite film conductivity that carbon nanotubes (CNTs) conductive nanonets are constructed from to provide fast carrier tracks. Resultantly, the CsPbBr3 nanosheet/CNT composite films exhibit both high light harvesting and high conductivity, such advantages are demonstrated by the high performances of corresponding planar PDs. Specifically, the highest external quantum efficiency (EQE) of 7488% and the highest responsivity of 31.1 A W-1 under a bias of 10 V among IHP PDs with planar structure are achieved, which are almost 125-fold over the previous best results. Besides, the efficient charge extraction and transport also remarkably contribute to the fast response speed where a rise time of 16 µs is achieved, which is also superior to state-of-the-art IHP PDs. Furthermore, the composite films exhibit impressive flexibility due to the ultrathin 2D and 1D structural characteristic of perovskites and CNTs. By deploying the PD as a point-like detector, we acquire clear images. The results indicate the promising potentials of the perovskite/CNT composites for solution and ambient condition processed flexible devices, and this strategy is general for all kinds of perovskite optoelectronic devices including photodetectors, phototransistors, and even LEDs.

Two-dimensional antimonene single crystals grown by van der Waals epitaxy.

Unlike the unstable black phosphorous, another two-dimensional group-VA material, antimonene, was recently predicted to exhibit good stability and remarkable physical properties. However, the synthesis of high-quality monolayer or few-layer antimonenes, sparsely reported, has greatly hindered the development of this new field. Here, we report the van der Waals epitaxy growth of few-layer antimonene monocrystalline polygons, their atomical microstructure and stability in ambient condition. The high-quality, few-layer antimonene monocrystalline polygons can be synthesized on various substrates, including flexible ones, via van der Waals epitaxy growth. Raman spectroscopy and transmission electron microscopy reveal that the obtained antimonene polygons have buckled rhombohedral atomic structure, consistent with the theoretically predicted most stable ß-phase allotrope. The very high stability of antimonenes was observed after aging in air for 30 days. First-principle and molecular dynamics simulation results confirmed that compared with phosphorene, antimonene is less likely to be oxidized and possesses higher thermodynamic stability in oxygen atmosphere at room temperature. Moreover, antimonene polygons show high electrical conductivity up to 104 S m-1 and good optical transparency in the visible light range, promising in transparent conductive electrode applications.

Complex deep lamellar endothelial keratoplasty for complex bullous keratopathy with severe vision loss.

PURPOSE: To determine the efficacy and postoperative complications of complex deep lamellar endothelial keratoplasty (DLEK) when used for the management of complex bullous keratopathy with severe vision loss. METHODS: Twelve consecutive eyes with severe bullous keratopathy and other associated intraocular abnormalities underwent complex DLEK which was combined with other intraocular surgeries such as vitrectomy, intraocular lens removal, and secondary intraocular lens implantation. An air bubble was used in 9 eyes and an air and C3F8 gas bubble in 3 eyes for tissue support. Prospective data of best spectacle-corrected visual acuity, corneal astigmatism, and curvature were collected on all 12 eyes preoperatively and at 6, 9, and 12 months postoperatively. Average donor endothelial cell density was recorded preoperatively and at 9 months postoperatively. RESULTS: Preoperatively, severe visual loss was recorded at hand motions (n = 3), count fingers (n = 7), and 20/400 (n = 2). Best spectacle-corrected visual acuity improved in 83% of eyes with vision of 20/67 or better in 42% (5/12) and 20/100 or better in 66% (8/12) of eyes at 12 months postoperatively. Vision was not improved in three eyes due to coexistent retinal disease. Four aphakic eyes underwent secondary intraocular lens implantation later at 4-6 months after DLEK, and best spectacle-corrected visual acuity was increased from count fingers to 20/200 or better. At 12 months postoperatively, average corneal astigmatism and curvature were 2.3 +/- 0.5 diopters and 44.0 +/- 0.9 diopters, respectively. Average central corneal thickness at 12 months postoperatively (541.3 +/- 26.7 microm) was significantly thinner than that before surgery (673.8 +/- 77.5 microm, P < 0.01). Preoperative average donor endothelial cell density was 2685.1 +/- 193.9 cells/mm. At 9 months postoperatively, average endothelial cell density was 1920.1 +/- 94.0 cells/mm (27.3% of endothelial cell loss) in eyes with primary surgery and 1866.3 +/- 92.8 cells/mm (33.9% of endothelial cell loss) in eyes with secondary surgery. Postoperative complications usually occurred within 3 months of surgery. After surgery, 3 eyes showed narrow gaps between the border of the graft and the host. Epithelial bullae in these areas recurred in 2 eyes but disappeared within 3 months. There was one graft dislocation in this series, no pupillary block cases, and no primary graft failures. CONCLUSIONS: In cases of complex bullous keratopathy with severe vision loss, DLEK combined with other intraocular surgeries is a feasible and effective procedure to significantly improve visual acuity to a functional level in most patients. DLEK can be used successfully in eyes with aphakia and other anterior segment abnormalities without a high risk of graft dislocation or failure. Mild postoperative complications usually occurred early after DLEK and did not affect visual outcomes and graft survival if managed appropriately.