Research progress on the mechanisms of microglia in retinal angiogenesis / 国际眼科杂志(Guoji Yanke Zazhi)

As resident immune cells of the retina, retinal microglia constantly monitor the changes of their surroundings and maintain homeostasis through signal transduction with other retinal cells. Retinal microglia play a crucial role not only in the development and physiological processes of the retinal vascular system, but also in pathological neovascularization. In certain retinopathies, activated microglia can stimulate abnormal angiogenesis through neurovascular coupling, leading to irreversible damage. However, the exact mechanisms underlying this process are still unclear. In this review, a brief overview of the relationship between microglia and retinal neovascularization was provided, and the involved cellular and molecular signaling mechanisms were reviewed, aiming to offer new and effective strategies for the prevention and treatment of retinal neovascularization diseases.

Application of Animal Models of Corneal Neovascularization Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo provide a reference for the establishment of an ideal corneal neovascularization （CNV） animal model by summarizing the modeling characteristics of CNV animal models. MethodWith "CVN" as the theme word， this paper searched the China National Knowledge Infrastructure （CNKI）， Wanfang， Chinese medical journals full-text database， and PubMed database and screened out relevant literature on CNV animal experiments from 2013 to 2023. The database was established by Excel 2021， and the experimental animal strain， gender， modeling method， detection index， and application category were sorted out. The characteristics of the CNV animal model were analyzed. ResultAfter comparative analysis， it was found that the animal strains were Sprague-Dawley rats （87 times， 29.49%） and New Zealand white rabbits （52 times， 17.63%）. Male animals were recommended. Most modeling methods for efficacy verification and mechanism studies were the alkali burn method. Index detection methods included apparent index observation， histopathological detection， immunohistochemistry （IHC）， Western blot， and various polymerase chain reaction （PCR） tests. Detection indexes included apparent indication， corneal histopathology， CNV regulation， etc. ConclusionThe CNV model of SD rats induced by the alkali burn method is recommended for model replication， and the indexes are mainly selected from the growth of CNV， corneal histopathological test， and vascular endothelial growth factor （VEGF）-related test. In addition， according to the demand， the corneal apparent indication and the basic indexes related to the regulation of CNV， such as vascular endothelial growth factor receptor 2 （VEGFR2）， basic fibroblast growth factor （bFGF）， and secretogranin Ⅲ （Scg3） are also selected. Clinical treatment of CNV relies on anti-inflammatory drugs and anti-VEGF drugs， and there is a lack of application of traditional Chinese medicine （TCM）， so the model needs to be improved by adding elements of TCM syndromes.

Research progress of microRNA in choroidal neovascularization signaling pathway / 国际眼科杂志(Guoji Yanke Zazhi)

Choroidal neovascularization(CNV)is the ultimate pathological manifestation of various ocular diseases. Its pathogenesis is extremely complex and involves multiple cells, cytokines, and signaling pathways. MicroRNA(miRNA), as a kind of small biological molecules, is a non-coding RNA composed of 22 nucleotides that regulates gene expression by degrading or inhibiting mRNA translation of target genes. Having been increasingly studied and their involvement in the development of various diseases through miRNA-mediated signaling pathways have been revealed. In the field of ophthalmology, miRNA target specific protein genes through various signaling pathways to promote or inhibit CNV. Therefore, revealing the role and mechanism of miRNA in the pathogenesis of CNV is an important direction of future research on the pathogenesis of CNV. This article aims to review on phosphatidylinositol 3 kinase- protein kinase B(PI3K-Akt), transforming growth factor-beta(TGF-β), nuclear factor-kappa B(NF-κB), Notch and Wnt signaling pathways in miRNA regulation of CNV, providing new insights into the pathogenesis of CNV and targeted therapy for CNV.

pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Profile of patients treated with intravitreal antiangiogenics in a Brazilian public service with high level of complexity / Perfil de pacientes tratados com antiangiogênicos intravítreo em serviço público brasileiro de alto nível de complexidade

ABSTRACT Purpose: Intravitreal antiangiogenic therapy is currently the most invasive ophthalmic procedure performed worldwide. This study aimed to describe the clinical and epidemiological profile of patients undergoing intravitreal antiangiogenic therapy in a tertiary referral hospital in Brazil. Methods: This cross-sectional, retrospective, and observational study analyzed medical records of patients who received intravitreal injections of antiangiogenic agents for the treatment of retinal diseases at the ophthalmology outpatient clinic in the Hospital das Clínicas at Unicamp between January and December 2020. Results: The study included 429 patients and 514 eyes. The study population was predominantly male (51.28%), white (80.89%), between 50 and 80 years old (mean age, 60.92 years), had complete or incomplete first-grade education (56.88%), and did not belong to the Regional Health Department of which Campinas is a part (78.55%). Bevacizumab was the most commonly used intravitreal injectable medicine (79.38%), pro re nata was the most commonly used treatment regimen (90.27%), and macular edema was the most prevalent pathology indicative of treatment (60.12%), with diabetes etiology accounting for 48.25%. The average number of injections per patient was 3.83, with the macular neovascularization group and the pro re nata group having the highest and lowest with five and three injections, respectively. Treatment adherence was associated with the patient's pathology, and the macular edema (52.24%) and macular neovascularization (49.48%) groups had the lowest adherence rates. Conclusions: This study evaluated the epidemiological and clinical profile of patients undergoing antiangiogenic therapy in a high-complexity public hospital, which is fundamental for a better understanding of the demand for ophthalmic reference service in Brazil, and the analysis of functional results and user adherence profile promotes optimization of indications and leverages the benefits of intravitreal therapy.

RESUMO Objetivo: A terapia antiangiogênica intravítrea revolucionou o tratamento de inúmeras patologias de relevância global, sendo atualmente o procedimento oftalmológico invasivo mais realizado no mundo. Objetiva-se no presente estudo descrever o perfil clínico e epidemiológico dos pacientes submetidos a terapia intravítrea com antiangiogênicos em hospital terciário de referência no Brasil. Métodos: Trata-se de um estudo transversal, retrospectivo e observacional que foi realizado através da análise de prontuários de pacientes submetidos a injeção intravítrea de antiangiogênicos para tratamento de doenças retinianas no ambulatório de oftalmologia do Hospital das Clínicas da Unicamp no período de janeiro a dezembro de 2020. Resultados: O estudo analisou 429 pacientes e 514 olhos. A maioria pertencia ao sexo masculino (51,28%), raça branca (80,89%), possuía entre 50-80 anos com idade média de 60,92 anos e escolaridade de 1º grau completo ou incompleto (56,88%) e não pertenciam (78,55%) a área de abrangência do Departamento Regional de Saúde do qual Campinas faz parte. O fármaco mais utilizado nas injeções intravítreas foi o bevacizumabe (79,38%), o principal regime de tratamento foi o pro re nata (90,27%) e a principal grupo de patologia indicativa de tratamento foi o edema macular (60,12%), sendo 48,25% desses de etiologia diabética. A média de injeções foi de 3,83/paciente, sendo o grupo de neovascularização macular o de maior mediana com 5 injeções/paciente e o esquema pro re nata o regime de tratamento com menor mediana, 3 injeções/paciente. A adesão ao tratamento associou-se a patologia do paciente, sendo as menores taxas de adesão as dos grupos com edema macular (52,24%) e neovascularização macular (49,48%). Conclusões: O presente estudo avaliou o perfil epidemiológico e clínico dos pacientes submetidos a terapia antiangiogênica em hospital público de alta complexidade, o que é fundamental para melhor conhecimento da demanda de serviço oftalmológico de referência no Brasil e possibilita, a partir da análise dos resultados funcionais e perfil de adesão dos usuários, otimizar as indicações e alavancar os benefícios de terapia intravítrea.

Partial regression of peripapillary myelinated nerve fibers after non-arteritic anterior ischemic optic neuropathy / Regressão parcial das fibras nervosas peripapilares mielinizadas após neuropatia óptica isquêmica anterior não arterítica

ABSTRACT A 71-year-old woman presented a non-arteritic anterior ischemic optic neuropathy in an optic nerve with previously registered superonasal peripapillary myelinated nerve fibers. Her past medical history was significant for controlled systemic hypertension, hyperlipidemia, and diabetes mellitus. The physiologic cup was absent in both optic discs. Non-arteritic anterior ischemic optic neuropathy mainly affected the temporal and inferior sectors of the peripapillary retinal nerve fiber layer, as could be demonstrated by retinal nerve fiber layer optical coherence tomography and optic disc optical coherence tomography angiography. Unlike other published reports, just a slight regression of the myelinated nerve fibers was observed after 1 year of follow-up. This occurred because ischemia mainly affected the temporal and inferior peripapillary sectors, whereas myelinated nerve fibers were superonasal to the optic disc.

RESUMO Uma mulher de 71 anos de idade apresentou neuropatia óptica isquêmica anterior não arterítica no nervo óptico com fibras nervosas peripapilares mielinizadas previamente registradas. Seu histórico médico foi significativo para hipertensão arterial sistêmica controlada, hiperlipidemia e diabetes mellitus. Em ambos os discos ópticos, a tacícula fisiológica esteve ausente. A neuropatia óptica isquêmica anterior não arterítica afetou principalmente os setores temporal e inferior da camada de fibras nervosas da retina peripapilar, como demonstrado pela tomografia de coerência óptica da camada de fibras nervosas da retina e pela angiotomografia de coerência óptica do disco óptico. Ao contrário de outros relatórios publicados, apenas uma ligeira regressão das fibras nervosas mielinizadas foi observada após um ano de acompanhamento. Isto pode ser explicado pelo fato da isquemia ter afetado principalmente os setores temporal e inferior peripapilares, enquanto as fibras nervosas de mielina eram nasal superior ao disco óptico.

Topographic distribution of retinal neovascularization in proliferative diabetic retinopathy using ultra-wide field angiography

Purpose: To analyze the topographic distribution of neovascularization (NV) and capillary nonperfusion (CNP) using ultra?wide field fluorescein angiography (UWFFA) in patients with proliferative diabetic retinopathy (PDR). Methods: This was a prospective, single?center, observational study in which all patients who presented between March 2019 and December 2020 and satisfied the inclusion criteria were recruited. In our study, patients with treatment?naïve PDR without any fibrovascular proliferation underwent UWFFA. The images were analyzed qualitatively for the topographic distribution of NV and the CNP area was quantified. The number of lesions picked by UWFFA was compared with 7 standard field (7SF) image using overlay of 7SF. The main outcome measure was characteristics of neovascularization, such as the number, location, and area of CNP, measured using UWFFA, which was considered with 95% confidence intervals (CI). Results: Two hundred and fifty?three eyes of 187 patients with a mean age of 56.03 ± 8 years were included. Mean neovascularization elsewhere (NVE) was 2.91 ± 3.43. Maximum NVEs were seen in the superotemporal (ST; 0.9 ± 1.13) quadrant, followed by the inferotemporal (IT; 0.7 ± 1.08), inferonasal (IN; 0.66 ± 1.02) and superonasal (SN; 0.66 ± 1.01) quadrants. Maximum CNP area was seen in the SN (13.75 ± 8.83 disc diameter square [DD2]) quadrant, followed by the IN (13.48 ± 8.59 DD2), IT (11.34 ± 8.37 DD2), and ST (11.3 ± 8.34 DD2) quadrants. Mean CNP area was maximum in patients with only neovascularization of disc (NVD; 64.99 ± 41.47 DD2), followed by both NVD and NVE (61.37 ± 35.61 DD2), and was minimum in patients with only NVE (36.44 ± 22.03 DD2). Eighty?one (32%) eyes out of 253 had NVE and 189 (75%) out of 253 had CNP area outside 7SF (overlay) of Early Treatment Diabetic Retinopathy Study (ETDRS). Conclusion: Diabetic NV lesions and CNP areas are distributed asymmetrically throughout the retina and are not restricted to the posterior pole. Compared to conventional 7SF imaging, UWFFA reveals significantly more retinal vascular pathology in patients with PDR.

Mechanism of curcumin inhibiting choroidal neovascularization in brown Norway rat / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the mechanism of curcumin inhibiting the choroidal neovascularization(CNV)of brown Norway(BN)rats.METHODS: CNV model of 36 BN rats was established through laser photocoagulation induction, and they were divided into 6 groups with 6 rats in each group. Normal group was fed normally with no intervention, while 532nm laser photocoagulation was used to establish a experimental CNV model in BN rats. Rats after modeling were respectively intervened for 14d and divided into model group, ranibizumab group, curcumin low [100mg/(kg·d)], medium [200mg/(kg·d)], and high [400mg/(kg·d)] dose group. The model group was given intragastric administration of saline for 14d, ranibizumab(10mg/mL, 0.2mL/dose)was injected at 2d after photocoagulation with 5μL once for rats in ranibizumab group, and different concentrations of curcumin were intragastrically administrated to the rats in low, medium and high groups for 14d. Fundus photography, fundus fluorescein angiography(FFA)and indocyanine green angiography(ICGA)examination were performed at 14d after photocoagulation. Ocular histopathological specimens of rats with CNV were made, and the central thickness of CNV were observed by HE staining. Ocular histopathological specimens were made, and the expressions of AKT/p-AKT/HIF-1α/VEGF signaling pathway-related proteins were observed by immunohistochemistry. The mRNA relative expressions of AKT/HIF-1α/VEGF factor in CNV tissues were detected by RT-qPCR, and the protein expressions of AKT/p-AKT/HIF-1α/VEGF factor in CNV tissues were detected by Western-blot.RESULTS: CNV generation rates in the model group, the ranibizumab group, and the low, medium and high-dose curcumin groups were 78.18%, 73.21%, 77.19%, 75.86%, 74.55%, respectively, which were higher than 70%. The average absorbance were 182.12±6.59, 119.22±8.03, 166.45±8.33, 164.34±5.69, 149.22±6.45, respectively; the ranibizumab group was significantly lower than the model group(P<0.05); the low-dose, medium-dose and high-dose groups were significantly higher than the ranibizumab group(P<0.05), and the curcumin high-dose group was significantly lower than the model group(P<0.05). HE staining showed that the retinal tissue structure of BN rats in normal group was clear and neatly arranged. The central thickness of CNV in the ranibizumab group was significantly reduced at 14d after photocoagulation compared with the model group(P<0.05); While the curcumin high-dose group was significantly reduced compared with the model group(P<0.05), but increased when compared with ranibizumab group(P<0.05). Immunohistochemistry results showed that AKT, p-AKT, HIF-1α, and VEGF factors were negatively expressed in the retinal tissue structure of BN rats in the normal group, and no brown-yellow reactants were found. The expression of AKT, p-AKT, HIF-1α, and VEGF factors in the model group were higher than that in the normal group at 14d after photocoagulation(P<0.05); the ranibizumab group was lower than the model group(P<0.05). While the expression of the curcumin high-dose group was significantly decreased compared with the model group(P<0.05), but significantly increased when compared with ranibizumab group(P<0.05). The mRNA results showed that the relative expression levels of AKT, HIF-1α and VEGF mRNA in the model group at 14d after photocoagulation were higher than those of the normal group(P<0.05); the ranibizumab group was lower than the model group(P<0.05). While curcumin high-dose group was significantly decreased compared with the model group(P<0.05), but significantly increased when compared with ranibizumab group(P<0.05). Western-blot results showed that there was no significant difference in the relative expression of AKT protein among each experimental groups at 14d after photocoagulation. The relative expression of p-AKT protein in the model group was significantly higher than that in the normal group(P<0.05); the ranibizumab group was significantly lower than the model group(P<0.05); the curcumin high-dose group was significantly lower than the model group(P<0.05). The relative expression levels of HIF-1α protein were significantly higher in the model group than in the normal group(P<0.05), and the ranibizumab group was lower than in the model group(P<0.05). The relative expression levels of HIF-1α protein was lower in the curcumin high-dose group than in the model group(P<0.05)but higher than ranibizumab group(P<0.05). The relative expression level of VEGF protein was significantly lower in the curcumin medium/high-dose group than in the model group(P<0.05).CONCLUSION: Curcumin at 400mg/(kg·d)has an inhibitory effect on CNV in BN rats. The mechanism may be closely related to inhibiting the activation of AKT/p-AKT/HIF-1α/VEGF signaling pathways.

Therapeutic effects of estrogen-intervened EPCs transplantation on diabetic ischemic stroke rats / 药学实践杂志

Objective To explore the therapeutic effects of estrogen-intervened endothelial progenitor cells( EPCs) transplantation on diabetic ischemic stroke rats. Methods PKH26-labeled diabetic EPCs and estrogen-intervened diabetic EPCs were injected into rats via the tail vein 24 h after cerebral ischemia. Cerebral ischemic volume, behavioral changes, ischemic site vascularization and homing of EPCs were measured 3 d after EPCs injection. Results Compared with diabetic ischemic rats, estrogen-intervened EPCs transplantation had reduced infarct volumes, improved behavioral scores and ischemic site revascularization and promoted homing of EPCs to sites of injury(P<0.05). Conclusion Estrogen-intervened EPCs transplantation had a better therapeutic effect on diabetic ischemic stroke by promoting EPCs homing to injury site and EPCs-medicated neovascularization .

Advances in corneal nerve regulation of ocular surface microenvironment / 国际眼科杂志(Guoji Yanke Zazhi)

The cornea is a transparent outer layer of the anterior eye segment, innervated by a high density of neural tissue. In the process of corneal innervation, trigeminal ganglion originated corneal nerves traverse different types of corneal cell in the epithelial and stromal layers. Corneal stromal cells, epithelial cells, immune cells, and other cells interact closely to maintain corneal microenvironmental homeostasis. In addition, corneal nerves is associated with the occurrence and development of many ocular surface diseases. Corneal nerves release various active peptides that regulate corneal sensation, maintain epithelial integrity and proliferation, improve wound healing, and manage local inflammation and immune response. This article reviews the advances in the corneal nerve regulation of the ocular surface microenvironment, providing some new ideas for the further study and treatment of corneal nerve-associated diseases.

Advances in Research Methods of Tumor Angiogenesis / 肿瘤防治研究

Nowadays, angiogenesis has gradually become one of the most popular research directions of cancer since Jodah Folkman put forward a theory about that tumor development needs angiogenesis. Meanwhile, relevant research methods are enriched step by step. In this paper, we have made a systematic review to provide methodological references for subsequent studies about tumor angiogenesis and antiangiogenic therapy.

Research advance on the role of hypoxia-inducible factor-1 in oxygen-induced retinal neovascularization / 中华实用儿科临床杂志

Hypoxia-inducible factor-1 (HIF-1) is an essential transcription factor, which mediates the transcription of multiple target genes to adapt the body for hypoxia.Oxygen-induced retinal neovascularization (RNV) is an important pathological process of retinopathy of prematurity (ROP). By mediating the transcription of vascular endothelial growth factors, angiopoietin and platelet-derived growth factors, HIF-1 can promote RNV and then lead to ROP.Therefore, HIF-1 plays a vital role in the pathological process of ROP.In this paper, the recent research progress on the role of HIF-1 in oxygen-induced RNV was summarized in order to further the understanding of ROP pathogenesis and treatment.

Experimental study of curcumol inhibiting vascular endothelial growth factor-induced neovascularization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the role and mechanism of curcumol in neovascularization induced by vascular endothelial growth factor(VEGF).METHODS: Human umbilical vein endothelial cells were cultured in vitro and treated with 50ng/mL VEGF and curcumol at different concentrations. Cell proliferation was detected by CCK-8 and EdU assay, the migration ability of cells was analyzed by Transwell assay, the angiogenesis ability of endothelial cells was analyzed by tube formation assay, and the change of Akt/mTORC1 signal pathway was detected by Western blot.RESULTS: CCK-8 results showed that the OD450 value of cells in 400 and 800 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(all P<0.01). EdU results showed that the rate of cell proliferation in 400 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(P<0.001). Transwell assay and the formation assay results showed that the number of migratory cells in 400 μmol/L curcumol+VEGF group was decreased, and the number and length of tube branches were also reduced compared with VEGF group(all P<0.001). Western blot results showed that curcumol significantly inhibited the expression of p-Akt and p-S6, which were downstream targets of Akt/mTORC1 pathway in cells.CONCLUSION: Curcumol can inhibit VEGF-induced cell proliferation, migration and tube formation of vein endothelial cells, and has a strong inhibitory effect on angiogenesis, which can be further studied in the treatment of ocular fundus neovascularization.

Correlation analysis of vision and changes of macular structure and microcirculation in myopic maculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the changes of macular morphology and microcirculation in myopic maculopathy(MM), and investigate theirs correlation and effects on vision.METHODS: Case-control study. A total of 165 patients(189 eyes)with high myopia and 154 healthy volunteers(154 eyes)from October 2016 to December 2018 were selected. According to the classification of Meta-analysis for pathologic myopia(META-PM), participants were divided into M0 group(category 0, 41 eyes), M1 group(category 1, 53 eyes), M2 group(category 2 and 3, 52 eyes), and myopic choroidal neovascularization(mCNV)group(43 eyes). All participants underwent optical coherence tomography angiography(OCTA)examination. Morphological and microcirculation parameters of retina at different layers were compared between groups. Pearson correlation was used to assess the correlation between morphological and microcirculation parameters. Correlations between vision and other parameters were analyzed using multiple linear regression analysis.RESULTS:Foveal full retinal thickness(FRT)and outer retinal thickness(ORT)were all lower in M0, M1 and M2 groups than those of control group(all P&#x003C;0.01). Foveal superficial capillary plexus vessel density(SVD)and deep capillary plexus vessel density(DVD)were all lower in M2 and mCNV groups than those of the control group(all P&#x003C;0.01). Parafoveal FRT and ORT were all lower in M0, M1, M2 and mCNV groups than those of the control group(all P&#x003C;0.01). Parafoveal inner retinal thickness(IRT), SVD and DVD were all lower in M2 and mCNV groups than those of the control group(all P&#x003C;0.01). Subfoveal choroidal thickness(SFCT)and choroid capillaries vessel density(CVD)were all lower in M0, M1, M2 and mCNV groups than those of the control group(all P&#x003C;0.01). Foveal vessel density of retina and choroid were positively correlated with its thickness in patients with MM without CNV(all P&#x003C;0.05). Multivariate analysis showed that axial length(AL), diffuse or patchy chorioretinal atrophy were influencing foctors of best corrected visual acuity(BCVA; all P&#x003C;0.01).CONCLUSION:Retinal morphological changes precede microcirculation changes in MM. Most of all, ORT changes precede IRT changes. Foveal vessel density of retina and choroid were positively correlated with its thickness. The main influencing factors of BCVA were AL and types of MM.

Influencing factors of poor response to anti-vascular endothelial growth factor drug therapy for wet age-related macular degeneration and therapeutic strategy of targeting pericytes / 国际眼科杂志(Guoji Yanke Zazhi)

With the increasing aging population, the incidence of wet age-related macular degeneration(wARMD)is gradually rising. The formation of neovascularization leads to recurrent hemorrhage in the macular region, which is one of the main causes of blindness in the elderly. Currently, the primary clinical treatment for wARMD is intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs. However, there are still some patients who have poor or no response to anti-VEGF drugs, resulting in suboptimal or ineffective clinical outcomes. Analyzing the specific influencing factors will be beneficial in guiding clinical decision-making. This article reviews the impact of factors such as advanced age, treatment duration, number of injections, characteristics of neovascular lesions, macular structure, intraocular cytokine levels, and genetics on the response to anti-VEGF therapy. In addition, recent studies have found that pericytes, as cellular components of microvascular walls, can influence the sensitivity to anti-VEGF therapy. This review summarizes the current research on the mechanisms of pericytes in poor or non-response to anti-VEGF therapy and discusses targeted strategies focusing on pericytes.

JAK-STAT signaling pathway and rosacea / 中华皮肤科杂志

Studies have shown that rosacea is related to inflammatory factors, neurovascular function, micro-ecological environment and other factors. The Janus kinase (JAK) -signal transducer and activator of transcription (STAT) signaling pathway involves a variety of inflammatory cytokines, and plays an important role in cell proliferation, differentiation, apoptosis, angiogenesis and immune regulation. This review summarizes the JAK-STAT signaling pathway and explores its potential role in rosacea.

The role of NLRP3/GATA-4/VEGF signal pathway in neovascular age-related macular degeneration / 中国医师杂志

Objective:To explore the potential role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/GATA-binding protein 4 (GATA-4)/vascular endothelial growth factor (VEGF) signal pathway in neovascular age-related macular degeneration (nAMD).Methods:We applied the TRANSFAC Public database to search the human and mouse VEGF promoters and upstream transcription factors, analyzed the transcription factors that may influence the transcriptional activity of VEGF. The RAW264.7 cells were divided into control group and lipopolysaccharide (LPS) stimulated group (LPS group). Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the activation of NLRP3 inflammasome, and the mRNA levels of GATA-4 and VEGFA. Thus, we applied the specific small molecular NLRP3 inhibitor MCC950 pretreated RAW264.7 cells (LPS+ MCC950 group), and detected the gene expression of NLRP3, Caspase-1, interleukin 1β( IL-1β), GATA-4 and VEGFA.Results:There were multiple GATA transcription factor binding sites upstream of human and mouse VEGF promoters. Compared with the control group, mRNA expression of NLRP3, Caspase-1, IL-1β, GATA-4 and VEGFA in LPS group were increased (all P<0.05). Compared with LPS group, mRNA expression of NLRP3, Caspase-1, IL-1β, GATA-4 and VEGFA in LPS+ MCC950 group were significantly decreased (all P<0.05). Conclusions:NLRP3/GATA-4/VEGF signal pathway may play a significant role in the pathologic processes of nAMD.

Effect and mechanism of curcumin on skin wound healing and angiogenesis in rats / 中国医师杂志

Objective:To investigate the effect of curcumin on skin wound healing and angiogenesis in rats and its possible mechanism.Methods:Rats with full-thickness dermal defect were prepared and randomly divided into model group, low-dose, medium-dose and high-dose groups of curcumin, with 10 rats in each group. Curcumin was injected intraperitoneally. The low-dose, medium-dose and high-dose groups of curcumin were given 5, 15, 45 mg/(kg·d) curcumin respectively. The rats in the model group were injected intraperitoneally with 0.5% sodium carboxymethyl cellulose for 14 days. The wound healing rate of rats in each group was measured; The wound tissue was stained with haematoxylin and eosin staining, Masson and immunohistochemistry; The levels of angiopoietin-1 (Ang-1) and basic fibroblast growth factor (bFGF) in the wound tissue of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA); The relative expression of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA in wound tissue was detected by real-time quantitative polymerase chain reaction (qRT-PCR); Western blot was used to detect the expression of VEGFA, VEGFR-2, Notch1, Jagged1, Hes1 protein in the wound tissue.Results:The wound healing rate, the vascular density and the level of Ang-1 and bFGF, the mRNA of VEGFA and VEGFR-2, the relative expression of Notch1, Jagged1, Hes1, VEGFA and VEGFR-2 protein in wound tissue of rats in low, medium and high dose groups of curcumin were higher than those in the model group (all P<0.05). Histological staining results showed that the reepithelialization of the wound tissue was not obvious in the model group, with severe infiltration of inflammatory cells and less collagen deposition; the reepithelialization of the wound tissue in the low-dose, medium-dose and high-dose groups of curcumin was gradually obvious, with thickened epidermis, reduced inflammatory cell infiltration and increased collagen deposition. The effect of curcumin on skin wounds in rats was enhanced in a dose-dependent manner (all P<0.05). Conclusions:Curcumin could promote wound healing and angiogenesis in rats, and its mechanism may be related to the activation of Notch signaling pathway.

Comparison of detection rates and time costs of different fundus imaging techniques for retinal neovascularization in optic disc and other area of proliferative diabetic retinopathy / 中华实验眼科杂志

Objective:To compare the detection rate and time cost of different imaging methods for retinal and optic disc neovascularization in proliferative diabetic retinopathy (PDR).Methods:A cross-sectional study was conducted.Thirty-eight patients (48 eyes) with PDR were enrolled in Henan Eye Hospital from October 2019 to February 2021, including 22 males (28 eyes) and 16 females (20 eyes). The average age of the patients was (51.08±13.35) years.All patients underwent ultra-widefield imaging (UWFI), fundus fluorescein angiography (FFA), optical coherence tomography angiography (OCTA), en face optical coherence tomography (OCT), near-infrared fundus imaging (IR) combined with spectral domain OCT (SD-OCT). Wide field swept-source OCTA (WF-SS-OCTA) was performed in the patients who were unsuitable for FFA.The time required for each examination in one eye and the detection rate of neovascularization at the optic disc (NVD) and retinal neovascularization elsewhere (NVE) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by Henan Eye Hospital (No.HNEECKY-2021[22]). All patients were informed about the method and purpose of the study and voluntarily signed the informed consent form.Results:The mean monocular examination time costs of UWFI, IR+ SD-OCT, OCTA+ en face OCT, FFA and WF-SS-OCT was (0.51±0.13), (2.08±0.57), (5.79±0.68), (17.66±1.83) and (13.38±1.23)min, respectively.There was a significant overall difference in the mean monocular examination time among the five methods ( F=2 077.960, P<0.001). The detection rates of UWFI, IR+ SD-OCT, OCTA+ en face OCT, FFA+ WF-SS-OCT for NVE and NVD were 52.1%(25/48) and 12.5%(6/48), 81.3%(39/48) and 20.8%(10/48), 83.3%(40/48) and 27.1%(13/48), 93.8%(45/48) and 29.2%(14/48), respectively.There were significant differences in the detection rates of NVE ( χ2=26.460, P<0.001) but not in the detection rates of NVD ( χ2=4.645, P=0.200) among the various methods.Five neovascular buds were detected by OCTA in 3 eyes, but not by FFA. Conclusions:UWFI and IR+ SD-OCT are faster and non-invasive methods for the screening of NVD and NVE in PDR eyes.Compared with FFA, OCTA and en face OCT can show the shape of neovascularization more clearly.FFA provides a wide-range retinal image, but it is time-consuming and invasive.WF-SS-OCTA extends the examination range of OCTA and detects neovascularization non-invasively and faster than FFA.

Progress in controlled ocular anti-VEGF drug release delivery system / 中华实验眼科杂志

Neovascularization is the hallmark of many fundus diseases, including diabetic retinopathy, retinal vein occlusion and neovascular age-related macular degeneration.More and more evidence suggests that vascular endothelial growth factor (VEGF) plays a critical role in neovascularization.Anti-VEGF drugs are the first-line treatment for neovascular fundus diseases and have achieved significant results.However, there are drawbacks such as short drug half-lives and the need for long-term administration to maintain effective concentrations, which increases the economic burden and medical risk for patients and reduces compliance.Therefore, finding a new method for intraocular drug delivery is of great clinical importance.Based on the principle that diabetes patients use insulin pumps to gradually release drugs, the ocular anti-VEGF drug delivery system can continuously release anti-VEGF drugs over a period of time, significantly reducing the injection frequency and improving patient compliance.At present, the research on ocular anti-VEGF drug delivery systems is still immature, and various systems are in different stages of clinical trials.According to different design principles, they can be divided into three categories with their characteristics, micropump (extraocular storage delivery systems), biodegradable implants, and non-biodegradable implants.This article summarized and analyzed the controlled ocular anti-VEGF drug release delivery systems currently in clinical trials.