The crosstalk between immune cells and tumor pyroptosis: advancing cancer immunotherapy strategies.

Pyroptosis is a cell death process characterized by cell swelling until membrane rupture and release of intracellular contents. As an effective tumor treatment strategy, inducing tumor cell pyroptosis has received widespread attention. In this process, the immune components within the tumor microenvironment play a key regulatory role. By regulating and altering the functions of immune cells such as cytotoxic T lymphocytes, natural killer cells, tumor-associated macrophages, and neutrophils, tumor cell pyroptosis can be induced. This article provides a comprehensive review of the molecular mechanisms of cell pyroptosis, the impact of the tumor immune microenvironment on tumor cell pyroptosis, and its mechanisms. It aims to gain an in-depth understanding of the communication between the tumor immune microenvironment and tumor cells, and to provide theoretical support for the development of new tumor immunotherapies.

Roles of Two-Dimensional Materials in Antibiofilm Applications: Recent Developments and Prospects.

Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such as those from the graphene family, boron nitride, molybdenum disulfide (MoS2), MXene, and black phosphorus, hold immense potential for combating biofilms. These nanomaterial-based antimicrobial strategies are novel tools that show promise in overcoming resistant bacteria and stubborn biofilms, with the ability to circumvent existing drug resistance mechanisms. This review comprehensively summarizes recent developments in two-dimensional nanomaterials, as both therapeutics and nanocarriers for precision antibiotic delivery, with a specific focus on nanoplatforms coupled with photothermal/photodynamic therapy in the elimination of bacteria and penetrating and/or ablating biofilm. This review offers important insight into recent advances and current limitations of current antibacterial nanotherapeutic approaches, together with a discussion on future developments in the field, for the overall benefit of public health.

In Situ Collection and SERS Detection of Nitrite in Exhalations on Facemasks Based on Wettability Differences.

As one of the common carriers of biological information, along with human urine specimens and blood, exhaled breath condensate (EBC) carries reliable and rich information about the body's metabolism to track human physiological normal/abnormal states and environmental exposures. What is more, EBC has gained extensive attention because of the convenient and nondestructive sampling. Facemasks, which act as a physical filter barrier between human exhaled breath and inhaled substances from the external environment, are safe, noninvasive, and economic devices for direct sampling of human exhaled breath and inhaled substances. Inspired by the ability of fog collection of Namib desert beetle, a strategy for in situ collecting and detecting EBC with surface-enhanced Raman scattering is illustrated. Based on the intrinsic and unique wettability differences between the squares and the surrounding area of the pattern on facemasks, the hydrophilic squares can capture exhaled droplets and spontaneously enrich the analytes and silver nanocubes (AgNCs), resulting in good repeatability in situ detection. Using R6G as the probe molecule, the minimal detectable concentration can reach as low as 10-16 M, and the relative standard deviation is less than 7%. This proves that this strategy can achieve high detection sensitivity and high detection repeatability. Meanwhile, this strategy is applicable for portable nitrite analysis in EBC and may provide an inspiration for monitoring other biomarkers in EBC.

TNFSF15 inhibits progression of diabetic retinopathy by blocking pyroptosis via interacting with GSDME.

Diabetic retinopathy is a common microvascular complication of diabetes and a leading cause of blindness. Pyroptosis has emerged as a mechanism of cell death involved in diabetic retinopathy pathology. This study explored the role of GSDME-mediated pyroptosis and its regulation by TNFSF15 in diabetic retinopathy. We found GSDME was upregulated in the progression of diabetic retinopathy. High glucose promoted GSDME-induced pyroptosis in retinal endothelial cells and retinal pigment epithelial cells, attributed to the activation of caspase-3 which cleaves GSDME to generate the pyroptosis-executing N-terminal fragment. TNFSF15 was identified as a binding partner and inhibitor of GSDME-mediated pyroptosis. TNFSF15 expression was increased by high glucose but suppressed by the caspase-3 activator Raptinal. Moreover, TNFSF15 protein inhibited high glucose- and Raptinal-induced pyroptosis by interacting with GSDME in retinal cells. Collectively, our results demonstrate TNFSF15 inhibits diabetic retinopathy progression by blocking GSDME-dependent pyroptosis of retinal cells, suggesting the TNFSF15-GSDME interaction as a promising therapeutic target for diabetic retinopathy.

Retinal Organoids: A Next-Generation Platform for High-Throughput Drug Discovery.

Retinal diseases are leading causes of blindness globally. Developing new drugs is of great significance for preventing vision loss. Current drug discovery relies mainly on two-dimensional in vitro models and animal models, but translation to human efficacy and safety is biased. In recent years, the emergence of retinal organoid technology platforms, utilizing three-dimensional microenvironments to better mimic retinal structure and function, has provided new platforms for exploring pathogenic mechanisms and drug screening. This review summarizes the latest advances in retinal organoid technology, emphasizing its application advantages in high-throughput drug screening, efficacy and toxicity evaluation, and translational medicine research. The review also prospects the combination of emerging technologies such as organ-on-a-chip, 3D bioprinting, single cell sequencing, gene editing with retinal organoid technology, which is expected to further optimize retinal organoid models and advance the diagnosis and treatment of retinal diseases.

A randomized non-inferiority trial of 577nm subthreshold micropulse laser versus half-dose photodynamic therapy for acute central serous chorioretinopathy.

PURPOSE: To compare the effectiveness of 577nm subthreshold micropulse laser (SML) with half-dose photodynamic therapy (Hd-PDT) for acute central serous chorioretinopathy (CSC). METHOD: A non-inferiority clinical trial was performed with a non-inferiority margin of eight letters. Sixty-eight eyes of 68 patients with acute CSC were randomized to the Hd-PDT group or 577 nm SML group. Best-corrected visual acuity (BCVA ), the subretinal fluid (SRF), and the central foveal thickness (CFT) were evaluated at 6 months. RESULTS: The visual acuity significantly improved from 70.38 ± 10.37 at baseline to 83.24 ± 3.03 at 6 months after treatment in the SML group (P < 0.001), from 71.09 ± 10.50 to 84.35 ± 2.09 in the PDT group (P < 0.001). SML was non-inferior to the PDT (mean difference: -0.41, 95% CI: -5.51 - 4.68, P = 0.0021). At the endpoint, CFT was significantly reduced in the two groups, but no statistical difference (P = 0.7694). The complete resolution of SRF reached 82.35% (28/34) in the SML group and 91.18% (31/34) in the PDT group, respectively,but no statistical difference (P = 0.3724). CONCLUSIONS: SML was non-inferiority to half-dose PDT in improving the visual acuity for CSC, and it is a viable alternative, especially when the verteporfin in PDT is unavailable.

Template-confined assembly of Ag nanocubes: An approach to fabricate SERS substrate with good performance.

Surface-enhanced Raman scattering (SERS) is an important analytical technique. Its detection sensitivity and reproducibility depend on the density and distribution of SERS hotspots. Self-assembly is an efficient method to produce of SERS substrates due to its easy accessibility. However, the assembled defects can hardly be avoided on large area, which could lower the density and uniformity of the hotspots, leading to poor SERS performance. Herein, we report a method to reduce the defects by taking a patterned substrate as template to confine the assembly of Ag nanocubes. The template was prepared based on the combination of photo lithography and self-assembly. Confined by the template, the Ag nanocubes were assembled closely in each dots of the pattern. The limit of detection (LOD) is down to 3.42 × 10-17 M and the enhanced factor (EF) is up to 3.44 × 1010 on the prepared substrate for detecting rhodamine 6G (R6G). In addition, the relative standard deviation (RSD) of the different substrates is 8.75 %. The assembled Ag nanocubes exhibits high sensitivity and reproducibility as SERS substrate, which are contributed by the formation of high-density and uniform hotspots. The prepared substrate can be used for detecting trace amounts of melamine in milk with LOD of 2.06 × 10-7 M and RSD of 6.91 %, so the substrate is applicable for analyzing various analytes.

Genome-wide association study on resistance of cultivated soybean to Fusarium oxysporum root rot in Northeast China.

BACKGROUND: Fusarium oxysporum is a prevalent fungal pathogen that diminishes soybean yield through seedling disease and root rot. Preventing Fusarium oxysporum root rot (FORR) damage entails on the identification of resistance genes and developing resistant cultivars. Therefore, conducting fine mapping and marker development for FORR resistance genes is of great significance for fostering the cultivation of resistant varieties. In this study, 350 soybean germplasm accessions, mainly from Northeast China, underwent genotyping using the SoySNP50K Illumina BeadChip, which includes 52,041 single nucleotide polymorphisms (SNPs). Their resistance to FORR was assessed in a greenhouse. Genome-wide association studies utilizing the general linear model, mixed linear model, compressed mixed linear model, and settlement of MLM under progressively exclusive relationship models were conducted to identify marker-trait associations while effectively controlling for population structure. RESULTS: The results demonstrated that these models effectively managed population structure. Eight SNP loci significantly associated with FORR resistance in soybean were detected, primarily located on Chromosome 6. Notably, there was a strong linkage disequilibrium between the large-effect SNPs ss715595462 and ss715595463, contributing substantially to phenotypic variation. Within the genetic interval encompassing these loci, 28 genes were present, with one gene Glyma.06G088400 encoding a protein kinase family protein containing a leucine-rich repeat domain identified as a potential candidate gene in the reference genome of Williams82. Additionally, quantitative real-time reverse transcription polymerase chain reaction analysis evaluated the gene expression levels between highly resistant and susceptible accessions, focusing on primary root tissues collected at different time points after F. oxysporum inoculation. Among the examined genes, only this gene emerged as the strongest candidate associated with FORR resistance. CONCLUSIONS: The identification of this candidate gene Glyma.06G088400 improves our understanding of soybean resistance to FORR and the markers strongly linked to resistance can be beneficial for molecular marker-assisted selection in breeding resistant soybean accessions against F. oxysporum.

Genome-wide association study of powdery mildew resistance in cultivated soybean from Northeast China.

Powdery mildew (PMD), caused by the pathogen Microsphaera diffusa, leads to substantial yield decreases in susceptible soybean under favorable environmental conditions. Effective prevention of soybean PMD damage can be achieved by identifying resistance genes and developing resistant cultivars. In this study, we genotyped 331 soybean germplasm accessions, primarily from Northeast China, using the SoySNP50K BeadChip, and evaluated their resistance to PMD in a greenhouse setting. To identify marker-trait associations while effectively controlling for population structure, we conducted genome-wide association studies utilizing factored spectrally transformed linear mixed models, mixed linear models, efficient mixed-model association eXpedited, and compressed mixed linear models. The results revealed seven single nucleotide polymorphism (SNP) loci strongly associated with PMD resistance in soybean. Among these, one SNP was localized on chromosome (Chr) 14, and six SNPs with low linkage disequilibrium were localized near or in the region of previously mapped genes on Chr 16. In the reference genome of Williams82, we discovered 96 genes within the candidate region, including 17 resistance (R)-like genes, which were identified as potential candidate genes for PMD resistance. In addition, we performed quantitative real-time reverse transcription polymerase chain reaction analysis to evaluate the gene expression levels in highly resistant and susceptible genotypes, focusing on leaf tissues collected at different times after M. diffusa inoculation. Among the examined genes, three R-like genes, including Glyma.16G210800, Glyma.16G212300, and Glyma.16G213900, were identified as strong candidates associated with PMD resistance. This discovery can significantly enhance our understanding of soybean resistance to PMD. Furthermore, the significant SNPs strongly associated with resistance can serve as valuable markers for genetic improvement in breeding M. diffusa-resistant soybean cultivars.

Spatial effects of the agricultural ecosystem services based on environmental kuznets curve in Mengyin county, China.

Worldwide most agroecosystems effort to increase production and yields and leads to damages of a series of non-provisioning ecosystem services (ESs). To fill in the knowledge gaps pertaining to the understanding of complex relationship between agricultural harvests and other ESs, therefore this study aims to estimate the existence of Environmental Kuznets Curve (EKC) for agricultural ESs by incorporating the spatial factors. Based on the test of the spatial autocorrelation of agricultural ESs, the estimation results of spatial model are compared with general regression to explain the spatial effect of agricultural ESs. The results show that (1) contrary to expectation, the curve of the nonlinear relationship between agricultural ESs and annual household income is an inverted U-shape, and not an upright U-shape; (2) compared to non-spatial model, the turning point of the inverted U-shaped curve for agricultural ESs under the direct effect would happen earlier and happen later under the indirect effect; (3) years of formal education, vegetation coverage of field margin and cultivated land area have significantly impact on local agricultural ESs, and local perennial crops has significantly impact on agricultural ESs of neighboring villages. Results of this study have a promising application prospect to promote sustainable development of agriculture.

Major genetic locus with pleiotropism determined seed-related traits in cultivated and wild soybeans.

KEY MESSAGE: Here, a novel pleiotropic QTL qSS14 simultaneously regulating four seed size traits and two consistently detected QTLs qSW17 and qSLW02 were identified across multiple years. Seed-related traits were the key agronomic traits that have been artificially selected during the domestication of wild soybean. Identifying the genetic loci and genes that regulate seed size could clarify the genetic variations in seed-related traits and provide novel insights into high-yield soybean breeding. In this study, we used a high-density genetic map constructed by F10 RIL populations from a cross between Glycine max and Glycine soja to detect additive QTLs for seven seed-related traits over the last three years. As a result, we identified one novel pleiotropic QTL, qSS14, that simultaneously controlled four seed size traits (100-seed weight, seed length, seed width, and seed thickness) and two consistently detected QTLs, qSW17, and qSLW02, in multiple years of phenotypic data. Furthermore, we predicted two, two and three candidate genes within these three critical loci based on the parental resequencing data and gene function annotations. And the relative expression of four candidate genes GLYMA_14G155100, GLYMA_17G061000, GLYMA_02G273100, and GLYMA_02G273300 showed significant differences among parents and the extreme materials through qRT-PCR analysis. These findings could facilitate the determination of beneficial genes in wild soybean and contribute to our understanding of the soybean domestication process.

Solubility and thermodynamic study of deferiprone in propylene glycol and ethanol mixture.

This work aims to obtain the solubility, density and thermodynamic parameters of deferiprone in propylene glycol and ethanol. For this purpose, a shake-flask technique was applied for solid-liquid equilibration and the spectrophotometry method was employed for solubility measurement. Solubility and density of deferiprone in non-aqueous mixtures of propylene glycol and ethanol were measured in the temperatures 293.2-313.2 K. Some equations including van't Hoff, the Jouyban-Acree, the Jouyban-Acree-van't Hoff, the mixture response surface and modified Wilson equations were used for the mathematical data modeling. The apparent thermodynamic parameters of the deferiprone dissolution process were computed and reported.

Retinal and Choroidal Alterations in Diabetic Retinopathy Treatment using Subthreshold Panretinal Photocoagulation with Endpoint Management Algorithm: A Secondary Analysis of a Randomized Clinical Trial.

INTRODUCTION: The aim of this study was to compare retinal and choroidal alterations in eyes with severe nonproliferative diabetic retinopathy (NPDR) after panretinal photocoagulation (PRP), using conventional pattern scan laser (PASCAL) and PASCAL with endpoint management (EPM). METHODS: This was a post hoc analysis of a paired randomized clinical trial. Bilateral treatment-naïve eyes of an individual with symmetric severe NPDR were randomly allocated into the threshold PRP group and subthreshold EPM PRP group. Patients had follow-up visits at 1, 3, 6, 9, and 12 months post-treatment. The retinal thickness (RT), choroidal thickness (CT), choroidal area, and choroidal vascularity index (CVI) were compared between the two groups and among different time points within the same group. RESULTS: Seventy eyes of 35 patients with diabetes mellitus (DM) were finally included for analysis at the 6- and 12-month visits, respectively. At 3 and 6 months post-treatment, the RT in the subthreshold EPM PRP group was significantly thinner than that in the threshold PRP group. CT, stromal area, and luminal area were reduced earlier in the threshold PRP group than in the subthreshold EPM PRP group. CVI was not significantly different within the same group or between groups at most time points. CONCLUSION: At 12 months post-treatment, retinal thickening and choroidal disturbance may be slightly less severe and more delayed in eyes receiving PRP using PASCAL with EPM than in those receiving PRP using conventional PASCAL. The EPM algorithm may be a good alternative in PRP when treating severe NPDR. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01759121.

Comparison of functional changes of retina after subthreshold and threshold pan-retinal photocoagulation in severe non-proliferative diabetic retinopathy.

PURPOSE: To find a new approach of pan-retinal photocoagulation (PRP) with less damage to the retina in the treatment of severe non-proliferative diabetic retinopathy (NPDR), this study compared functional changes in the retina after subthreshold and threshold PRP treatment in severe NPDR eyes. METHODS: Post hoc analysis of a randomized clinical trial was conducted in this study. Seventy eyes of 35 patients with bilateral, symmetric, severe NPDR were enrolled. Two eyes from the same patient were randomized into two groups, one eye received subthreshold PRP (S-PRP) and the other eye received threshold PRP (T-PRP). Comprehensive ophthalmological evaluations were performed on the baseline and every 3 months for 1 year. Visual field (VF) and full-field electroretinography (ERG) were performed on the baseline and repeated at month 12. RESULTS: During the 12-month follow-up, 4 eyes (11.4%) in the S-PRP group and 3 eyes (8.6%) in the T-PRP group progressed to proliferative diabetic retinopathy (PDR) stage, and there was no statistical difference in PDR progression rate between the two groups (P = 0.69). In addition, the changes in best-corrected visual acuity (BCVA) from baseline to month 12 between the two groups had no statistical difference (P = 0.30). From baseline to month 12, changes in central VF between the two groups had no statistical difference (P = 0.25), but changes in total score points of peripheral VF in the S-PRP group (- 242.1 ± 210.8 dB) and the T-PRP group (- 308.9 ± 209.7 dB) were statistically significant (P = 0.03). At month 12, ERG records showed that the amplitude of dark-adapted 0.01 ERG, dark-adapted 3.0 ERG, oscillatory potentials, light-adapted 3.0 ERG, and 30 Hz flicker ERG of both groups were significantly decreased from the baseline (P < 0.05). In addition, the amplitude of each ERG record in the S-PRP group decreased significantly less than those in the T-PRP group (P < 0.05). CONCLUSIONS: Subthreshold PRP is as effective as threshold PRP for preventing severe NPDR progress to PDR within 1 year with less damage to periphery VF and retinal function. CLINICALTRIALS: gov Identifier: NCT01759121.

Identification of genetic loci conferring seed coat color based on a high-density map in soybean.

Seed coat color is a typical evolutionary trait. Identification of the genetic loci that control seed coat color during the domestication of wild soybean could clarify the genetic variations between cultivated and wild soybean. We used 276 F10 recombinant inbred lines (RILs) from the cross between a cultivated soybean (JY47) and a wild soybean (ZYD00321) as the materials to identify the quantitative trait loci (QTLs) for seed coat color. We constructed a high-density genetic map using re-sequencing technology. The average distance between adjacent markers was 0.31 cM on this map, comprising 9,083 bin markers. We identified two stable QTLs (qSC08 and qSC11) for seed coat color using this map, which, respectively, explained 21.933 and 26.934% of the phenotypic variation. Two candidate genes (CHS3C and CHS4A) in qSC08 were identified according to the parental re-sequencing data and gene function annotations. Five genes (LOC100786658, LOC100801691, LOC100806824, LOC100795475, and LOC100787559) were predicted in the novel QTL qSC11, which, according to gene function annotations, might control seed coat color. This result could facilitate the identification of beneficial genes from wild soybean and provide useful information to clarify the genetic variations for seed coat color in cultivated and wild soybean.

Predicting Central Serous Chorioretinopathy Recurrence Using Machine Learning.

Purpose: To predict central serous chorioretinopathy (CSC) recurrence 3 and 6 months after laser treatment by using machine learning. Methods: Clinical and imaging features of 461 patients (480 eyes) with CSC were collected at Zhongshan Ophthalmic Center (ZOC) and Xiamen Eye Center (XEC). The ZOC data (416 eyes of 401 patients) were used as the training dataset and the internal test dataset, while the XEC data (64 eyes of 60 patients) were used as the external test dataset. Six different machine learning algorithms and an ensemble model were trained to predict recurrence in patients with CSC. After completing the initial detailed investigation, we designed a simplified model using only clinical data and OCT features. Results: The ensemble model exhibited the best performance among the six algorithms, with accuracies of 0.941 (internal test dataset) and 0.970 (external test dataset) at 3 months and 0.903 (internal test dataset) and 1.000 (external test dataset) at 6 months. The simplified model showed a comparable level of predictive power. Conclusion: Machine learning achieves high accuracies in predicting the recurrence of CSC patients. The application of an intelligent recurrence prediction model for patients with CSC can potentially facilitate recurrence factor identification and precise individualized interventions.

Deep Learning for Detecting Subretinal Fluid and Discerning Macular Status by Fundus Images in Central Serous Chorioretinopathy.

Subretinal fluid (SRF) can lead to irreversible visual loss in patients with central serous chorioretinopathy (CSC) if not absorbed in time. Early detection and intervention of SRF can help improve visual prognosis and reduce irreversible damage to the retina. As fundus image is the most commonly used and easily obtained examination for patients with CSC, the purpose of our research is to investigate whether and to what extent SRF depicted on fundus images can be assessed using deep learning technology. In this study, we developed a cascaded deep learning system based on fundus image for automated SRF detection and macula-on/off serous retinal detachment discerning. The performance of our system is reliable, and its accuracy of SRF detection is higher than that of experienced retinal specialists. In addition, the system can automatically indicate whether the SRF progression involves the macula to provide guidance of urgency for patients. The implementation of our deep learning system could effectively reduce the extent of vision impairment resulting from SRF in patients with CSC by providing timely identification and referral.

Comparison of the Effect of Pan-Retinal Photocoagulation and Intravitreal Conbercept Treatment on the Change of Retinal Vessel Density Monitored by Optical Coherence Tomography Angiography in Patients with Proliferative Diabetic Retinopathy.

BACKGROUND: This study compares the change of retinal vessel density (VD) after pan-retinal photocoagulation (PRP) and intravitreal conbercept (IVC) treatment in proliferative diabetic retinopathy (PDR) eyes with optical coherence tomography angiography (OCTA). METHODS: A total of 55 treatment-naïve PDR eyes were included in this retrospective study. Of these, 29 eyes were divided into a PRP group, and 26 eyes were divided into an IVC group based on the treatment they received. OCTA was performed to measure macular and papillary VD at each follow-up in both groups. RESULTS: The macular VD for superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC) and papillary VD for radial peripapillary capillary (RPC) between the two groups demonstrated no significant difference at baseline and month 12 (p > 0.05). The paired t-test results showed that the macular VD for SCP, DCP, CC and papillary VD for the RPC at month 12 did not differ to the baseline in each group (p > 0.05). CONCLUSIONS: During the 12-month follow-up, there was no significant change of macular and papillary VD between the PRP and IVC treatment in PDR eyes. Additionally, compared to the baseline, there were no significant changes of macular and papillary VD after either the PRP or IVC treatment. Considering the decrease in VD as DR progress, both treatments have potential protection of macular and papillary VD loss in PDR.

Intravitreal injection of triptolide attenuates subretinal fibrosis in laser-induced murine model.

BACKGROUND: Choroidal neovascularization (CNV) is a common cause of irreversible blindness in elderly patients in developed countries, and subretinal fibrosis is an advanced stage of CNV. Currently, there is no effective clinical treatment for subretinal fibrosis. PURPOSE: To investigate whether intravitreal injection of triptolide (TP) could attenuate subretinal fibrosis and determine its underlying mechanisms. METHODS: CNV was induced by laser photocoagulation in C57BL/6J mice. Immediately after laser photocoagulation, 1 µl of free TP (10 µg), TP-nanolip-PEG (TP-loaded PEGylated nanoliposomes containing 10 µg TP), or the same volume of phosphate-buffered saline (PBS) was intravitreally administered to each respective group. Areas and ratios of subretinal fibrosis were calculated seven days after laser injury. Additionally, expression levels of M2 macrophage-related markers, molecules of the transforming growth factor (TGF)-ß1/Smad signaling pathway, and markers for epithelial-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT) were detected both in vitro and in vivo. RESULTS: The areas of subretinal fibrosis were significantly reduced in both the free TP (10993.87 ± 2416.90 µm2) and TP-nanolip-PEG (7695.32 ± 2121.91 µm2) groups when compared with the PBS group (15971.97 ± 3203.10 µm2) (p < 0.05, n = 6). The ratio of subretinal fibrosis in the free TP monomer (20.8 ± 4.2%) and TP-nanolip-PEG (12.5 ± 4.0%) groups was lower than that in the PBS control group (41.7 ± 5.3%) (p < 0.01, n = 6). Moreover, both TP and TP-nanolip-PEG suppressed the polarization of M2 macrophages and downregulated gene expressions of TGF-ß1, Smad 2, Smad 3, α-SMA, and collagen I (p < 0.05), but upregulated the gene expression of E-cadherin (p < 0.05), thus reversing TGF-ß1 induced EMT/EndoMT and attenuating subretinal fibrosis. CONCLUSIONS: TP could attenuate subretinal fibrosis by suppressing the polarization of M2 macrophages and TGF-ß1 induced EMT/EndoMT. TP-nanolip-PEG enhanced the inhibitory effects of TP on subretinal fibrosis, suggesting its therapeutic potential for CNV-related subretinal fibrosis.

Quantitative evaluation of damage to retinal capillaries caused by half-dose and half-time photodynamic therapy with optical coherent tomographic angiography.

PURPOSE: To determine and compare retinal capillaries damage in patients with chronic central serous chorioretinopathy (CSC) after half-dose and half-time photodynamic therapy (PDT) based on optical coherence tomographic angiography (OCTA). METHODS: Thirty-three eyes of 33 patients and 32 eyes of 32 patients with active CSC were treated with half-dose PDT and half-time PDT respectively and followed up for 3 months. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed at baseline; best corrected visual acuity (BCVA) and OCTA were performed at baseline, 3-day, 7-day, 14-day, 1-month, and 3-month follow-up visits. RESULTS: Twenty-eight patients in half-dose group and 27 patients in the half-time group finished the 3-month follow-up visits. BCVA was significantly improved at post-PDT 1 month and 3 months (both P < 0.05) and central macula thickness (CMT) was significantly decreased at all post-PDT time points (all P < 0.05) in both groups. 22 patients (78.57%) in the half-dose group and 21 patients (77.78%) in the half-time group had complete absorption of subretinal fluid (SRF) at post-PDT 3 months. There was no significant difference in the above-mentioned prognostic measurements between two groups. The mean vessel densities of superficial retina (VDSR) and inner retina (VDIR) layers were decreased at all post-PDT time points in both groups. However, the decrease of VDIR and VDSR at post-PDT 3 days and 3 months in the half-dose group was much severe than those in the half-time group (P < 0.05). CONCLUSIONS: Both half-dose and half-time modifications of PDT were similarly effective in improving the BCVA and decreasing the SRF for chronic CSC. However, the retinal capillaries damage in the half-time group was less severe than that in the half-dose group, so the half-time modification may be a more appropriate parameter for patients with chronic CSC.