Purpose:In ischemic retinopathy (IR), hypoxia-inducible factor (HIF)-1α contributes to vision-threatening pathological retinal neovascularization (RNV). This study investigated the therapeutic efficacy and action mechanisms of the newly developed HIF-1α inhibitor IDF-11774 for IR in hypoxia-exposed human umbilical vein endothelial cells (HUVECs) and human retinal microvascular endothelial cells (HRMECs), as well as an oxygen-induced retinopathy (OIR) model mice. Methods:The effect of IDF-11774 on HIF-1α expression in HUVECs was assessed by quantitative real-time polymerase chain reaction (RT-qPCR), immunoblotting, and immunostaining, and effects on angiogenic potential were evaluated by cell proliferation, scratch wound, Transwell, and tube formation assays. Pathological RNV and vascular permeability were analyzed by immunostaining, hematoxylin and eosin staining, and dye leakage assays on postnatal day (P)17 following intravitreal injection of IDF-11774 (18.4 ng) or vehicle at P12. Target genes were identified by RNA sequencing and validated by western blot and immunostaining. Electroretinography, TUNEL staining, and immunofluorescence staining were conducted to evaluate the retinal toxicity of intravitreal IDF-11774. Results:In HUVECs, IDF-11774 inhibited hypoxia-induced HIF-1α expression through proteasomal degradation and concomitantly suppressed proliferation, migration, and tube formation. In OIR mice, IDF-11774 significantly reduced RNV, facilitated revascularization in the vascular obliterated zone, and alleviated vascular leakage. The key vascular regulatory signaling pathways ANGPT2/TIE2 and PlGF were modulated by IDF-11774 in hypoxic HUVECs and HRMECs, as well as in OIR mice. High-dose IDF-11774 had no significant effects on the electroretinogram or retinal histology. Conclusions:Inhibiting HIF-1α with IDF-11774 exerts multiple therapeutic and pathway-regulatory effects and demonstrates a favorable retinal safety profile, highlighting IDF-11774 as a potentially therapeutic strategy for IR.

The distinct spatiotemporal characteristics of the hourly intense precipitation (HIP) over the Pearl River Delta (PRD) and the impact of urbanization before and after the monsoon onset from 1972 to 2021 have been investigated using the hourly rain gauge data, nighttime lights data, and land use data. The results show a significant decreasing trend of HIP during the pre-monsoon onset period and a notable increasing trend during the post-monsoon onset period over the past five decades. However, compared to rural areas, rapid urbanization in the PRD after the mid-1990s weakens the HIP reduction, especially in the inland cities of PRD before the onset of the monsoon and enhances the HIP increase, particularly in the southeast inland and west coast cities after the onset of the monsoon. After rapid urbanization, the peak time of HIP has been postponed from 14 LST to 17 LST during the pre-monsoon onset period. HIP tends to occur more frequently in urban areas in the morning (10-12 LST) and evening (19-24 LST) compared to rural areas. In contrast, the impact of urbanization on the diurnal variation of HIP is not obvious during the post-monsoon period, despite higher frequencies of HIP occurring during the daytime (10-15 LST) in the urban areas after rapid urbanization. These findings provide valuable insights for forecasting HIP in urban agglomerations.

Purpose: The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying mechanisms. Methods: In this study, we utilized a model of laser-induced CNV in both young (3 months old) and old (18 months old) mice, including those with or without Sema4D knockout. The expression and localization of Sema4D in CNV were assessed using PCR, Western blot, and immunostaining. Subsequently, the morphological and imaging examinations were used to evaluate the size of CNV and vascular leakage. Finally, the expression of M2 markers, senescence-related markers, and molecules involved in the RhoA/ROCK pathway was detected. Results: We found that Sema4D was predominantly expressed in macrophages within CNV lesions, and both the mRNA and protein levels of Sema4D progressively increased following laser photocoagulation, a trend more pronounced in old mice. Moreover, Sema4D knockout markedly inhibited M2 polarization in senescent macrophages and reduced the size and leakage of CNV, particularly in aged mice. Mechanistically, aging was found to upregulate RhoA/ROCK signaling, and knockout of Sema4D effectively suppressed the activation of this pathway, with more significant effects observed in aged mice. Conclusions: Our findings revealed that the deletion of Sema4D markedly inhibited M2 macrophage polarization through the suppression of the RhoA/ROCK pathway, ultimately leading to the attenuation of senescence-associated CNV. These data indicate that targeting Sema4D could offer a promising approach for gene editing therapy in patients with neovascular age-related macular degeneration.

The study explores the characteristics of morning extreme precipitation (MEP) during the pre-summer in inland Guangdong. Based on the principal modes, MEP events can be classified into four groups. The first group of MEP (G1) is a typical southeastward-propagating rainfall system originating from the northwestern mountains. This is caused by the strongest accelerated southwesterly winds at night, which bring abundant moist and warm air from the South China Sea (SCS) along with the shear line and the highest convective available potential energy (CAPE). The second group of MEP (G2) is warm-sector heavy rainfall with large-scale warming and higher CAPE. This local rainfall system originates in the south of Nanling mountains at night and reaches its mature stage in the morning. The rainfall system of the third group (G3) originates in central Guangxi and propagates to the southern inland region. The southeasterly winds in Guangxi intensify at night due to the anomalous cyclonic circulation. However, in the morning, the easterly winds shift to the westerlies, favoring eastward propagation. After SCS monsoon onset, cold air intrudes southward, colliding with moist warm air from the SCS, leading to heavy frontal precipitation in the inland region, classified as the fourth group MEP (G4).

Based on multiple datasets, a comparative analysis has investigated the different rainfall distributions and the factors related to strong (weak) rainfall induced by landfalling strong typhoons moving northwest (SR-NWLFSTYs, WR-NWLFSTYs) which are defined from the tracks, the locations, and intensities of the rainfall center of LFSTYs based on a dynamic composite analysis method. The obviously stronger rainfall induced by SR-NWLFSTYs, with the intensive rainfall center presenting a cyclonic rotation in the lifecycle of typhoons, tends to be accompanied by the pronouncedly enhanced low-level jet and a warmer SST before and during landfall. Owing to the enhanced low-level jet, moisture convergence experiences an intensification, resulting in a warmer and more humid circulation. Sufficient water vapor and latent heat is favorable for the enhancement of the mid-troposphere warm core structure with longer maintenance which can prolong the impact period of typhoons, leading to continuous precipitation. Simultaneously, the coupling of low-level convergence and upper-level divergence provides favorable dynamic conditions, thus further promoting the upward transportation of moisture through Ekman pumping, which tends to increase the mid-troposphere moisture through moisture advection. The changes in the mid-troposphere moisture coincide well with the evolution of rainfall over the same region during the lifecycle of typhoons. Comparatively, the asymmetric rainfall features of WR-NWLFSTYs with intense rainfall center mainly placed in the northeast quarter of the TC center during the lifecycle of TCs is likely related to the relatively weaker low-level jet which remains almost constant during and after landfall. The weaker low-level flow transports less moisture into the cyclone, and prohibits the weakening of vertical wind shear after landfall, leading to reduced precipitation with an obvious asymmetric distribution. Concurrently, the configuration of the weakening upper-level divergence and low-level convergence after landfall has been unable to maintain the upward motion for precipitation, resulting in relatively weaker rainfall for WR-NWLFSTYs.

The presummer intense regional rainfall events (RREs) over the Pearl River Delta (PRD) metropolitan region have been defined using rainy stations, maximum instantaneous regional rainfall coefficient (RRCt) and maximum rainfall intensity based on the rain gauge data from 2008 to 2017. Most of intense RREs with the maximum rainfall intensity about 20-60 mm.h(-1) and the lifetime shorter than 24 h have the primary rainfall peak from noon to afternoon. Based on the rainfall pattern at 3 h prior to the events start, the intense RREs can be classified into two groups that one is southeastward propagation mode originating from the northwestern mountains of PRD and another is coastal mode from South China Sea (SCS). During the premonsoon-onset period, the first type of RREs is the main mode causing the heavy rain in the cities of the inland region owing to the anomalous cold air from north confronting the wet and warm air from south with the increased southwesterly winds resulting in the strengthening frontal zone and moisture convergence. After the summer monsoon onset, the main rainfall pattern changes to the coastal mode having the significant impact on the coastal cities. The obvious anomalous cyclonic circulation related with the increased moisture convergence in the coastal regions providing the favourable conditions of the convection initiation and development. The study of the characteristics and evolution process of preceding intense RREs can improve the forecasting skills and reduce the risk of urban inundation.

Purpose:To evaluate differences in the choroidal vortex vein drainage system (VV) in eyes between patients with central serous chorioretinopathy (CSC) and unaffected individuals using ultra-widefield optical coherence tomography angiography (UWF-OCTA).Methods:In this cross-sectional observational study, 40 eyes of patients with CSC and 28 eyes of healthy volunteers were included. The analysis involved the use of UWF-OCTA to analyze the proportion of the choroidal vortex vein drainage system (VV%), choroidal thickness, choroidal vascular volume (CVV), and choroidal vascularity index (CVI) of the VV in each drainage quadrant. The location relationship between the leakage points in fluorescein angiography and the VV was also explored.Results:A within-group analysis of VV% showed a statistically significant difference in the CSC group (P < 0.001) but not in the control group (P = 0.270). Compared to healthy eyes, CSC eyes had a significantly larger CVV and higher CVI in all regions (all P < 0.05). The superotemporal (ST) drainage system had the largest CVV and thickest choroidal layer among the four drainage quadrants (all P < 0.05) in CSC eyes. The leakage rate in the ST quadrant was significantly higher than that in the inferotemporal quadrant (P < 0.001).Conclusions:CSC eyes have an asymmetric vortex vein drainage system, with relative hyperperfusion in all VV. Further, the preferential drainage route of the submacular choroid may be the ST drainage system in CSC eyes.Translational Relevance:Targeting the imbalanced drainage system could be a potential therapeutic approach for CSC.

Central serous chorioretinopathy (CSC) is a vision-threatening disease with no validated treatment and unclear pathogenesis. It is characterized by dilation and leakage of choroidal vasculature, resulting in the accumulation of subretinal fluid, and serous detachment of the neurosensory retina. Numerous studies have demonstrated that melatonin had multiple protective effects against endothelial dysfunction, vascular inflammation, and blood-retinal barrier (BRB) breakdown. However, the effect of melatonin on CSC, and its exact pathogenesis, is not well understood thus far. In this study, an experimental model was established by intravitreal injection of aldosterone in rats, which mimicked the features of CSC. Our results found that melatonin administration in advance significantly inhibited aldosterone-induced choroidal thickening and vasodilation by reducing the expression of calcium-activated potassium channel KCa2.3, and attenuated tortuosity of choroid vessels. Moreover, melatonin protected the BRB integrity and prevented the decrease in tight junction protein (ZO-1, occludin, and claudin-1) levels in the rat model induced by aldosterone. Additionally, the data also showed that intraperitoneal injection of melatonin in advance inhibited aldosterone-induced macrophage/microglia infiltration, and remarkably diminished the levels of inflammatory cytokines (interleukin-6 [IL-6], IL-1 beta, and cyclooxygenase-2), chemokines (chemokine C-C motif ligand 3, and C-X-C motif ligand 1), and matrix metalloproteinases (MMP-2 and MMP-9). Luzindole, as the nonselective MT1 and MT2 antagonist, and 4-phenyl-2-propionamidotetraline, as the selective MT2 antagonist, neutralized the melatonin-induced inhibition of choroidal thickening and choroidal vasodilation, indicating that melatonin might exert the effects via binding to its receptors. Furthermore, the IL-17A/nuclear factor-kappa B signaling pathway was activated by intravitreal administration of aldosterone, while it was suppressed in melatonin-treated in advance rat eyes. This study indicates that melatonin could serve as a promising safe therapeutic strategy for CSC patients.

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 β-galactosidase (SA-β-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-β-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.

Purpose KC7F2 is a novel molecule compound that can inhibit the translation of hypoxia-inducible factor 1α (HIF1α). It has been reported to exhibit potential antiangiogenic effect. We hypothesized that KC7F2 could inhibit oxygen-induced retinal neovascularization (RNV). The purpose of this study was to investigate this assumption. Methods Oxygen-induced retinopathy (OIR) models in C57BL/6J mice and Sprague-Dawley rats were used for in vivo study. After intraperitoneal injections of KC7F2, RNV was detected by immunofluorescence and hematoxylin and eosin staining. Retinal inflammation was explored by immunofluorescence. EdU incorporation assay, cell counting kit-8 assay, scratch test, transwell assay, and Matrigel assay were used to evaluate the effect of KC7F2 on the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVEC) induced by vascular endothelial growth factor (VEGF) in vitro. Protein expression was examined by Western blot. Results KC7F2 treatment (10 mg/kg/d) in OIR mice significantly attenuated pathological neovascularization and decreased the number of preretinal neovascular cell nuclei, without changing the avascular area, which showed the same trends in OIR rats. Consistently, after the KC7F2 intervention (10 µM), cell proliferation was inhibited in VEGF-induced HUVEC, which was in agreement with the trend observed in the retinas of OIR mice. Meanwhile, KC7F2 suppressed VEGF-induced HUVEC migration and tube formation, and decreased the density of leukocytes and microglia colocalizing neovascular areas in the retinas. Moreover, the HIF1α–VEGF pathway activated in retinas of OIR mice and hypoxia-induced HUVEC, was suppressed by KC7F2 treatment. Conclusions The current study revealed that KC7F2 was able to inhibit RNV effectively via HIF1α–VEGF pathway, suggesting that it might be an effective drug for RNV treatment.

In this study, the convection‐permitting model (CPM) with 3‐km horizontal resolution has been used to investigate the simulated ability on diurnal cycles of pre‐summer rainfall over southern China with various subregions and rainfall systems. Compared with the observations, the model captures the peak time of nocturnal rainfall in the western inland related to the eastward‐propagating rainfall system over the eastern slope of the Yungui Plateau. The simulated eastward‐propagating rainfall system moves a short distance and has a short lifetime due to the weaker westerly‐steering flow and southerly winds in the late night bringing less warm and moist air with the weaker upward flow of the mountain–plain solenoid circulation that is unfavorable for convection instability. Over the eastern inland, the model shows good performance on simulating the quasi‐stationary rainfall system in the morning because of the high resolution of topography. However, the model cannot simulate the climatology of the secondary morning rainfall peak due to overestimation of the rainfall from noon to evening. On the other hand, the weaker simulated southwesterly winds especially on the north side of the Nanling Mountains with decreased upward movement and moisture convergence and the more stable atmospheric condition lead to the disadvantage of convective rainfall. The CPM reproduces the afternoon rainfall peak but with a lead of 2–3 hr and still cannot simulate the morning peak well over the coastal region. The main source of mode bias is the overestimation of the onshore winds in the boundary layer over the land with the reduced temperature difference between land and sea resulting in insufficient convergence in the coastal region.

Retinopathy of prematurity is a vision-threatening disease associated with retinal hypoxia-ischemia, leading to the death of retinal neurons and chronic neuronal degeneration. During this study, we used the oxygen-induced retinopathy mice model to mimic retinal hypoxia-ischemia phenotypes to investigate further the neuroprotective effect of melatonin on neonatal retinal neurons. Melatonin helped maintain relatively normal inner retinal architecture and thickness and preserve inner retinal neuron populations in avascular areas by rescuing retinal ganglion and bipolar cells, and horizontal and amacrine neurons, from apoptosis. Meanwhile, melatonin recovered visual dysfunction, as reflected by the improved amplitudes and implicit times of a-wave, b-wave, and oscillatory potentials. Additionally, elevated cleaved caspase-3 and Bax protein levels and reduced Bcl-2 protein levels in response to hypoxia-ischemia were diminished after melatonin treatment. Moreover, melatonin increased BDNF and downstream phospho-TrkB/Akt/ERK/CREB levels. ANA-12, a TrkB receptor antagonist, antagonized these melatonin actions and reduced melatonin-induced neuroprotection. Furthermore, melatonin rescued the reduction in melatonin receptor expression. This study suggests that melatonin exerted anti-apoptotic and neuroprotective effects in inner retinal neurons after hypoxia-ischemia, at least partly due to modulation of the BDNF-TrkB pathway.

OBJECTIVE:Microglia/macrophage activation is previously reported to be involved in various ocular diseases. However, the separate role of M1/M2 phenotype microglia/macrophage in the pathological process of oxygen-induced retinopathy (OIR) remains unknown. In this research, we explored the role and regulatory mechanism of M1/M2 microglia/macrophage in OIR in C57BL/6J mice. Furthermore, we demonstrated the time phase of M1/M2 shifting of microglia/macrophage during the natural process of OIR, which is very essential for further investigations.MATERIALS AND METHODS:C57BL/6j pups were exposed to hyperoxia environment from postnatal 7(P7) to P12 then returned to normoxia. The mice were then euthanized, and the eyes were harvested at a series of time points for further investigation. The M1/M2 phenotype microglia/macrophage activity was presented by immunofluorescent staining and real-time quantitative polymerase chain reaction (qPCR). The NF-κb-STAT3 signaling and IL-4-STAT6-PPAR-γ signaling pathway activity was examined by western blot analysis.RESULTS:The microglia/macrophage were activated when the OIR model was set up after P12. The M1 microglia/macrophage activation was found in neovascularization (NV) tufts in both central and peripheral retina, which started from P12 when the mice were returned to normoxia environment and peaked at P17. During this period of time, the NF-κb-STAT3 signaling pathway was activated, resulting in the upregulated M1 phenotype microglia/macrophage polarization, along with the enhanced inflammatory cytokine expression including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β. Consequently, the NV tufts were observed from P12 and the volume continued to increase until P17. However, the M2 phenotype microglia/macrophage activity took over during the late phase of OIR started from P17. The IL-4-STAT6-PPAR-γ signaling activity was upregulated from P17 and peaked at P20, inducing M2 phenotype microglia polarization, which consequently led to the inhibition of inflammatory cytokines and spontaneous regression of NV tufts.CONCLUSIONS:Microglia/macrophage participate actively in the natural process of OIR in mice, and two phenotypes exert different functions. Treatment modulating microglia/macrophage polarize toward M2 phenotype might be a novel and promising method for ocular neovascular diseases such as retinopathy of prematurity (ROP), wet age-related macular degeneration (wAMD), and diabetic retinopathy (DR).

PURPOSE:To investigate the expression of CD146 and its role in proliferative diabetic retinopathy (PDR).METHODS:Enzyme linked immunosorbent assay was performed to analyse the expression and relationship of sCD146, vascular endothelial growth factor (VEGF), sVEGFR1 and sVEGFR2 in vitreous specimens from PDR and idiopathic epiretinal membranes (IERM) or idiopathic macular hole patients. The location of CD146 in ERMs was detected by immunofluorescence. The oxygen-induced retinopathy (OIR) mice model was established and the adeno-associated virus expressing a shRNA of CD146 (AAV1-shCD146-GFP) was administered via intravitreal injection. The effect of AAV1-shCD146-GFP was explored by immunofluorescence, Western blot and quantitative real-time PCR.RESULTS:The levels of sCD146 in vitreous specimens from PDR patients and CD146 in retinas from OIR mice were significantly increased. Immunofluorescence showed that CD146 was co-located with CD31, VEGF, VEGFR1 and VEGFR2, respectively. Intravitreal injection of AAV1-shCD146-GFP could dramatically reduce the formation of neovascularization and non-perfusion area by inhibiting VEGFR2 phosphorylation.CONCLUSION:Our results indicated that CD146 was involved in the development of retinal neovascularization via VEGFR2 pathway. Anti-CD146 may be an innovative or adjuvant therapy, which provides a new direction for the treatment of PDR and other ocular neovascular diseases.

Diabetic macular edema (DME) is one of the most frequent causes of severe vision loss. The pathogenesis of DME is still not fully understood; however, it is hypothesized to result from breakdown of the blood–retinal barrier (BRB) due to retinal inflammation by vascular endothelial growth factor (VEGF) secretion under hyperglycemic conditions. In this investigation, we discovered that Prolyl-4-hydroxylase 2 (PHD2), an upstream regulator of hypoxia-inducible factor 1 (HIF-1) modulates VEGF expression and thus preserves BRB function in the mouse retina. Primary human retinal microvascular endothelial cells (hRMECs) were cultured in human endothelial serum-free growth medium and exposed to hyperglycemia. Changes in cell viability were investigated by an MTT assay. BRB function in each group was revealed by a paracellular permeability assay and trans-endothelial electrical resistance (TEER). Morphological changes in the BRB were investigated by immunofluorescence staining of occludin and zonula occludens-1 (ZO-1). The mRNA and protein levels of the tight junction proteins, PHD2, HIF-1α, and VEGF were measured by reverse transcription-quantitative PCR (RT-qPCR), western blot analysis and ELISA. Under hyperglycemic conditions, the viability of hRMECs was decreased, and PHD2 expression was downregulated, accompanied by increased paracellular permeability and decreased trans-endothelial electrical resistance. Additionally, HIF-1α and VEGF expression levels were increased, whereas the expression levels of tight junction proteins, including occludin and ZO-1, were decreased and BRB function was compromised. The PHD2 activator R59949 (diacylglycerol kinase inhibitor II), altered these pathological changes, and the PHD2 inhibitor dimethyloxalylglycine (DMOG) resulted in the opposite effects. These results demonstrated that PHD2 inhibited HIF-1 activity by inhibiting HIF-1α expression in hRMECs under hyperglycemic conditions, which led to the downregulation of the expression of the angiogenic factor VEGF, and thus helped to maintain the functions of hRMECs. Therefore, it is reasonable to propose that PHD2 could be a potential novel target for the treatment of DME or other diseases with a similar pathogenesis.

Choroidal neovascularization (CNV) is an important characteristic of advanced wet age‐related macular degeneration (AMD) and leads to severe visual impairment among elderly patients. Previous studies have demonstrated that melatonin induces several biological effects related to antioxidation, anti‐inflammation, and anti‐angiogenesis. However, the role of melatonin in CNV, and its underlying mechanisms, has not been investigated thus far. In this study, we found that melatonin administration significantly reduced the scale and volume of CNV lesions, suppressed vascular leakage, and inhibited the capacity of vascular proliferation in the laser‐induced mouse CNV model. Additionally, the results also show that the melatonin‐treated retinal microglia in the laser‐induced mice exhibited enhanced expression of M1‐type markers, such as iNOS, CCL‐3, CCL‐5, and TNF‐α, as well as decreased production of M2‐type markers, such as Arg‐1, Fizz‐1, IL‐10, YM‐1, and CD206, indicating that melatonin switched the macrophage/microglia polarization from pro‐angiogenic M2 phenotype to anti‐angiogenic M1 phenotype. Furthermore, the RhoA/ROCK signaling pathway was activated during CNV formation, yet was suppressed after an intraperitoneal injection of melatonin. In conclusion, melatonin attenuated CNV, reduced vascular leakage, and inhibited vascular proliferation by switching the macrophage/microglia polarization from M2 phenotype to M1 phenotype via inhibition of RhoA/ROCK signaling pathway in CNV. This suggests that melatonin could be a novel agent for the treatment of AMD.

Purpose: To investigate vasculature-function and structure-function relationship in healthy myopic eyes using optical coherence tomography angiography (OCT-A), optical coherence tomography (OCT) and microperimetry (MAIA). Methods: A total of 370 eyes from 190 participants were enrolled in this study. Subjects divided into three groups based on refractive status: low myopia (LM) (-3.00D <= spherical equivalent, SE <= -0.50D), moderate myopia (MM) (-6.00D <= SE < -3.00D) and high myopia (HM) (SE < -6.00D). The vessel density (VD), retinal thickness (RT) and light sensitivity (LS) were evaluated using OCT-A, OCT and MAIA. The global and regional vasculature-function and structure-function relationship were evaluated by the semi-partial correlation analysis according to ETDRS grid. The uni- and multivariate linear regression models were performed using LS as the dependent variable and covariates, included age, gender, intraocular pressure (IOP), axial length (AL), SE, ganglion cell complex thickness (GCCT), superficial (SVD) and deep vessel density (DVD) and RT as independent variables. Results: The LS negatively correlated with AL and positively correlated with SE, DVD, RT and GCCT (P < .05). The DVD was associated with the corresponding LS only in temporal and nasal sectors in HM (sr: 0.182-0.195, P < .05) but SVD not at all. The RT was associated with the corresponding LS in inferior and nasal sectors in MM (sr: 0.221-0.281, P < .005) and all sectors in HM (sr: 0.187-0.229, P < .05). Lower DVD and RT were independently associated with the declined LS in myopic eyes (P < .05). Conclusions: Reduced DVD and RT were independently associated with the declined LS in healthy myopic eyes, especially in HM.

This study evaluates 32 climate models from CMIP5 compared with a daily griddedobservation dataset of extreme precipitation indices including total extreme precipitation (R95p),maximum consecutive five days of precipitation (RX5day) and wet days larger than 10 mm ofprecipitation (R10mm) over Northern China during the historical period (1986–2005). Results showthe majority models have good performance on spatial distribution but overestimate the amplitude ofprecipitation over Northern China. Most models can also capture interannual variation of R95p andRX5d, but with poor simulations on R10mm. Considering both spatial and temporal factors, the bestmulti-model ensemble (Group 1) has been selected and improved by 42%, 34%, and 37% for R95p,RX5d, and R10mm, respectively. Projection of extreme precipitation indicates that the fastest-risingregion is in Northwest China due to the enhanced rainfall intensity. However, the uncertaintyanalysis shows the increase of extreme rainfall over Northwest China has a low confidence level.The projection of increasing extreme rainfall over Northeast China from Group 1 due to the longerextreme rainfall days is more credible. The weak subtropical high and southwest winds from ArabianSea lead to the low wet biases from Group 1 and the cyclonic anomalies over Northeast China, whichresult in more extreme precipitation.