Genetic variations of IL10 and IL6R genes in acute anterior uveitis in Han Chinese.

BACKGROUND: Several autoimmune disorders have been linked to polymorphisms in IL10 and IL6R genes. This research aimed to study whether single nucleotide polymorphisms (SNPs) in the genes of IL10 and IL6R were associated with acute anterior uveitis (AAU) in Han Chinese. METHODS: Genotyping was carried out by the iPLEX Gold Genotyping Assay. Our study comprised 420 patients with AAU and 918 healthy subjects from Han Chinese. Using the chi-square (χ2) test, alleles and genotypes were analyzed between AAU subjects and healthy controls. RESULTS: All ten SNPs were successfully genotyped and four SNPs (IL10/rs1800871, IL10/rs3021094, IL10/rs2222202, IL6R/rs4845618) exhibited weak associations with AAU, as indicated by their Puncorr values. However, upon applying the Bonferroni correction, there was no significant association between AAU and the control subjects. Additionally, the haplotype analysis of the ten SNPs revealed no association with AAU. CONCLUSION: Our findings suggested that polymorphisms of the tested ten SNPs on the IL10 and IL6R genes did not show any association with the risk of developing AAU among the Han Chinese population.

Correlation of TBX21 gene polymorphisms with ankylosing spondylitis in a Chinese population.

Genome-wide association studies analysis has revealed associations between ankylosing spondylitis (AS) and loci on the TBX21 gene across various populations. This study aimed to investigate if there is a connection between a higher risk of AS in a Chinese population and two polymorphism loci on the TBX21 gene. To achieve this, we performed a case-control investigation involving 363 patients with AS and 907 healthy individuals. Genotyping was carried out using the iPLEX Gold genotyping assay. The analysis of genotypes and haplotypes was performed using SPSS 23.0 and SHEsis software. The results revealed no statistically significant correlation between the two specified single-nucleotide polymorphisms of TBX21 (rs11657479 C/T and rs4794067 C/T) and susceptibility to AS. However, upon conducting stratification analysis, our findings demonstrated a significant association between rs11657479 and susceptibility to human leucocyte antigen (HLA)-B27+ AS in allelic (C vs. T: odds ratio [OR] = 1.52, 95%CI = 1.09-2.11, corrected p [pc] = .028), heterozygous (CT vs. TT: OR = 1.63, 95%CI = 1.13-2.34, pc = .016) and dominant (CT + CC vs. TT: OR = 1.60, 95%CI = 1.12-2.28, pc = .018) models. Furthermore, the haplotype rs4794067/C-rs11657479/C of TBX21 was found to increase the risk of HLA-B27+ AS cases. In conclusion, our findings indicate a correlation between TBX21 gene polymorphism and HLA-B27+ AS patients within the Chinese population.

Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease.

Introduction: Disulfidptosis is a recently identified form of cell death that contributes to maintaining the internal environment balance of an organism. However, the molecular basis of disulfidptosis in ulcerative colitis (UC), ankylosing spondylitis (AS), and Crohn's disease (CD) has not been thoroughly explored. Methods: Firstly, the differentially expressed genes (DEGs) and disulfidptosis-associated genes (DAGs) were obtained through differential analysis between diseases (AS, CD, and UC) and control groups. After the disulfidptosis score was acquired using the single-sample gene set enrichment analysis (ssGSEA) algorithm, the DE-DAGs were screened by overlapping DAGs and DEGs of the three diseases. Next, the feature genes were selected through a combination of machine learning algorithms, receiver operating characteristic (ROC) curves, and expression analysis. Based on these feature genes, nomograms were created for AS, CD and UC. The co-feature genes were then identified by taking the intersections of the genes featured in all three diseases. Meanwhile, single-gene set enrichment analysis (GSEA) and the TF-mRNA-miRNA network were utilized to investigate the molecular mechanisms of the co-feature genes. To validate the expression differences of the co-feature genes between healthy controls and patients (AS and IBD), RT-PCR was performed. Lastly, mendelian randomization (MR) analysis was utilized to explore the causality between genetic variants of S100A12 with AS, UC and CD. Results: In this study, 11 DE-DAGs were obtained. Functional enrichment analysis revealed their involvement in cytokine production and fatty acid biosynthesis. Latterly, AS/CD/UC -feature genes were derived, and they all had decent diagnostic performance. Through evaluation, the performance of the nomogram was decent for three diseases. Then, 2 co-feature genes (S100A12 and LILRA5) were obtained. The GSEA enrichment results indicated that the co-feature genes were mainly enriched in the cytokine-cytokine receptor interaction and drug metabolism cytochrome P450. As shown by functional experiments, there was a correlation between the mRNA expression of S100A12 with AS, UC and CD. Additionally, a causal connection between S100A12 and IBD was detected through MR analysis. Discussion: In this study, 2 co-feature genes (S100A12 and LILRA5) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment.

Associations of IL6R and IL10 Gene Polymorphisms with Susceptibility to Ankylosing Spondylitis with or without Acute Anterior Uveitis.

BACKGROUND: This research aims to explore the associations between ten candidate single nucleotide polymorphisms (SNPs) on Interleukin-6 receptor (IL6R) and Interleukin-10 (IL10) genes and ankylosing spondylitis (AS) patients with or without acute anterior uveitis (AAU). METHODS: This study involved a case-control approach that examined 354 cases with AS and AAU, 377 AS cases without AAU, and 918 healthy controls. Genotyping of ten SNPs of IL10 and IL6R genes was performed using iPLEX Gold genotyping method. The allele and genotype frequencies of cases and healthy individuals were contrasted using the chi-square test. The IL10 mRNA level in various IL10 genotypes was tested using real-time PCR. RESULTS: Two loci associated with AS with AAU were identified: IL10//rs3790622 (OR = 0.664; 95%CI = 0.503-0.878; Pc = 0.038); IL10//rs3021094 (OR = 1.365; 95%CI = 1.110-1.679; Pc = 0.032). The other eight loci located on IL10 and IL6R did not show significant associations with the diseases. Additionally, as shown by functional experiments, there was no correlation between the mRNA expression of IL10 and various genotypes. CONCLUSION: Our study suggests that the IL10 gene contributes to the susceptibility of the Chinese population to AS with AAU.

The SNTB1 and ZFHX1B gene have susceptibility in northern Han Chinese populations with high myopia.

The aim of this study was to explore the association between SNTB1 and ZFHX1B polymorphisms and high myopia (HM) in a Northern Han Chinese population. This case-control study included 457 HM and 860 healthy subjects from the Northern Han Chinese population. Four single nucleotide polymorphisms (SNPs) (rs7839488, rs4395927, rs4455882, and rs6469937) in SNTB1 and one SNP in ZFHX1B (rs13382811)were selected based on two previous genome-wide association study (GWAS) studies. The allele and genotype distributions of SNPs in SNTB1 and ZFHX1B were compared between the two groups using the chi-square test. The allele results were adjusted for age and sex using Plink software (Plink 1.9). Pairwise linkage disequilibrium (LD) and haplotype analyses were performed using SHEsis software. For HM subjects, the mean age was 44.80 ± 17.11 years, and for the control subjects, it was 44.41 ± 14.26 years. For rs7839488 of the SNTB1 gene, the A allele is a risk allele and the G allele is a wild allele. The A allele had no statistical significance with the HM cases and controls (OR = 0.90, 95% CI = 0.74-1.09, aP = 0.273, Pc = NS). There was a LD in SNTB1 (rs7839488, rs4395927, rs4455882, and rs6469937). The G-C-A-G haplotype frequency was higher in HM subjects than that of the controls (OR = 1.31, 95% CI = 1.07-1.60, P = 0.008). Meanwhile, the A-T-G-A haplotype frequency was slightly lower in the HM group (OR = 0.81, 95% CI = 0.66-0.99, P = 0.048). In the ZFHX1B gene, the frequency of the minor T allele of rs13382811 was significant higher in the HM group than in the control group (OR = 1.34, 95% CI = 1.11-1.61, aP = 0.001, Pc = 0.009). Furthermore, compared to the CC genotype, there were significant differences in the CT genotype (OR = 1.57, 95% CI = 1.23-2.00, aP < 0.001, Pc = 0.002). In conclusion, G-C-A-G is a risk haplotype from the SNTB1 gene in high myopia patients. The minor T-allele of ZFHX1B rs13382811 is a risk factor for high myopia. SNTB1 and ZFHX1B are both risk genes associated with increased susceptibility to high myopia in the Northern Han Chinese population.

Relationship between Uveitis and the Differential Reactivity of Retinal Microglia.

Uveitis, a complicated group of ocular inflammatory diseases, can be affected by massive pathogenic contributors such as infection, autoimmunity, and genetics. Although it is well known that many pathological changes, including disorders of the immune system and disruption of the blood-retinal barrier, count much in the onset and progression of uveitis, there is a paucity of safe and effective treatments, which has exceedingly hindered the appropriate treatment of uveitis. As innate immune cells in the retina, microglia occupy a salient position in retinal homeostasis. Many studies have reported the activation of microglia in uveitis and the mitigation of uveitis by interfering with microglial reactivity, which strongly implicates microglia as a therapeutic target. However, it has been increasingly recognized that microglia are a nonhomogeneous population under different physiological and pathological conditions, which makes it essential to thoroughly have knowledge of their specific characteristics. The paper outlines the various properties of activated microglia in uveitis, summarizes the connections between their polarization patterns and the manifestations of uveitis, and ultimately is intended to enhance the understanding of microglial versatility and expedite the exploration of promising strategies for visual protection.

Evaluation of myopia-associated genes in a Han Chinese population with high myopia.

BACKGROUND: High myopia is a leading cause of blindness worldwide. However, the exact etiology and mechanism of high myopia remain unclear. Previous genome-wide association study has demonstrated that nine single nucleotide polymorphisms (SNPs) in East and Southeast Asian populations were associated with high myopia and proved that the nervous system was involved in the pathogenesis of high myopia. The present study was conducted to investigate whether these genetic variants retinal nervous system-related were associated with high myopia among Han Chinese. METHODS: Seven SNPs were genotyped by the MassARRAY iPLEX Gold method in a Han Chinese cohort with the majority from Henan region (central China), which included 361 patients with high myopia and 749 healthy controls. RESULTS: In terms of genotyped SNPs, the allele frequency of rs698047 locus of the HIVEP3 gene were statistically different between myopia and control groups initially, but the difference disappeared after Bonferroni method correction. When the genetic model analysis was performed, the rs698047 locus additive model 2 of the HIVEP3 gene was found to be different between the case and control groups in the Han Chinese population (Pc = 0. 049, OR = 1.64, 95% CI 1.14-2.36). CONCLUSIONS: There was no demonstrated association between the occurrence of high myopia in the Chinese Han population and polymorphisms in the following loci: HIVEP3 (rs698047), NFASC/CNTN2 (rs2246661), ZC3H11B (rs12032649), CNTN4/CNTN6 (rs17029206), FRMD4B (rs74633073), AKAP13 (rs72748160), and GJD2 (rs589135).

The correlation of endoplasmic reticulum aminopeptidase 1 polymorphisms with Behçet's disease: a meta-analysis.

OBJECTIVES: Substantial evidence has highlighted the mediation of endoplasmic reticulum aminopeptidase 1 (ERAP1) in the onset of Behçet's disease (BD), which can be differentially converted by ERAP1 variants. To comprehensively elaborate this issue, we undertook the meta-analysis to estimate the liaison of ERAP1 polymorphisms with BD risk. METHODS: Literatures were retrieved in a standardised fashion and data underwent multi-perspective analyses utilizing STATA Statistical Software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) of manifold comparisons between BD sufferers and healthy masses were exploited to evaluate the extent of relevance. RESULTS: Overall analyses suggested that the meanings of ERAP1 polymorphisms in BD susceptibility varied among plentiful variations, where rs10050860, rs17482078, rs2287987, rs1065407 and rs72773968 presented pathogenic influence and rs26618 acted out beneficial function, while rs27044, rs26653, rs27895 and rs3734016 had no pronounced biological significance. Additionally, the effect of rs30187 is not yet determined. Moreover, race appeared a crucial ingredient as Mongolian were more susceptible to suffering from BD than Caucasian, while the diagnostic criteria of BD exerted a relative inconspicuous role, where the International Study Group criteria slightly attenuated the pathogenicity of ERAP1 polymorphisms compared with the International Criteria for Behçet's Disease. Finally, an exceeding importance was attached to the proceeding analysis based on disparities in BD symptoms, ERAP1 haplotypes and HLA-B*51 in computing the hazard zonation of ERAP1 polymorphisms on BD tendency. CONCLUSIONS: The present meta-analysis prompted the heterogeneous influences of ERAP1 polymorphisms on BD development, which were malleable under the discrepancies in genetic grounds and disease diagnoses.

Extreme myopia is more susceptible to SOX2 gene than high myopia.

PURPOSE: To explore the association between two single-nucleotide polymorphisms (SNPs) in the SOX2 gene and high and extreme myopia in the Han Chinese population. MATERIALS AND METHODS: A genetic association study using a case-control method was performed with 139 high myopia, 318 extreme myopia, and 918 healthy participants from the Chinese Han population. Two SNPs (rs4459940 and rs4575941) near SOX2 gene were selected for genotyping. We compared the allelic frequencies and haplotypes of the SNPs to assess their association with high and extreme myopia. This study was adjusted for sex and age of participants in the groups. RESULT: The mean ages of the extreme myopia and control subjects were 47.44 ± 15.59 and 44.15 ± 14.08 years, respectively. The rs4575941 SNP of the SOX2 gene and the GG and AG genotypes showed no significant association with the risk of high myopia as opposed to the AA genotype (GG, OR = 0.94, 95% CI = 0.55-1.60, P = 0.820, Pc = NS; AG, OR = 0.91, 95% CI = 0.54-1.52, P = 0.708, Pc = NS). However, the frequency of the risk G allele of rs4575941 was significantly higher in the extreme myopia group than in the control group (OR = 1.31, 95% CI = 1.08-1.59; P = 0.007; Pc = 0.014). Furthermore, there were significant differences in the GG genotype frequency between the extreme myopia and control groups (OR = 1.77, 95% CI = 1.45-2.74, P = 0.009, Pc = 0.036). The A-G haplotype frequency was higher in the extreme group (OR = 1.27, 95% CI = 1.05-1.55, P = 0.014), while there were no significant differences found in high myopia group (OR = 1.18, 95% CI = 0.77-1.31, P = 0.979). CONCLUSION: The SOX2 rs4575941 polymorphism, in Chinese Han population, contributes to the susceptibility of extreme myopia. SOX2 may thus be implicated in extreme myopia rather than in high myopia.

COVID-19 pandemic impact on ocular trauma in a tertiary hospital.

AIM: To analyze the impact of the coronavirus disease-2019 (COVID-19) pandemic on the presentation and characteristics of patients hospitalized for ocular trauma in a tertiary hospital in China between 2019 and 2020. METHODS: A retrospective case study was designed to collect information on all cases of ocular trauma in a tertiary hospital from 2019 to 2020 and compare differences in inpatients' data (age, sex, admission vision acuity, type of diagnosis, hospital stays, mechanism of injury and location of injury). RESULTS: The total number of patients admitted to the Ophthalmology Department was 883 (mean 73.58±11.25 patients per month) in 2019 and 714 (59.50±17.92 patients per month) in 2020. The injury number of in work was also the most within the four types of location in this two year (42.36% in 2019, 43.84% in 2020). The mean hospital stays were 12.66d in 2019 and 10.81d in 2020. The highest incidence of ocular trauma was the middle-aged (41-65y) groups in 2019 and 2020. The most common cause of ocular trauma was sharp object in 2019 (47.34%) and 2020 (47.58%). The mechanical ocular trauma reaches 98.98% in 2019 and 99.72% in 2020. CONCLUSION: The number of patients with ocular trauma decreased in 2020, but middle-aged (41-65y) are still high incident groups. Mechanical ocular trauma remains the leading cause of hospitalization for ocular trauma patients and the proportion of patients injured at home increases. It is necessary to arouse social attention and the public's awareness of eye trauma protection should be strengthened during the pandemic.

Peripheral complete blood cell count indices and serum lipid levels in polypoidal choroidal vasculopathy.

CLINICAL RELEVANCE: Systemic inflammation factors (e.g. white blood cells and neutrophils), high level of triglyceride and high neutrophil-to-lymphocyte ratio have significant associations with the risk of polypoidal choroidal vasculopathy (PCV). BACKGROUND: This study aimed to investigate associations of complete blood cell count-derived indicators and serum lipid levels with PCV. METHODS: Forty-eight patients with PCV and 54 age- and gender-matched control group participants were included in the study. Records of demographic characteristics and the results of ophthalmic examinations and haematologic parameters for the participants were collected retrospectively. Blood cell count-derived indicators and serum lipid levels were calculated and were compared between the two groups. RESULTS: The PCV group had higher white blood cell, neutrophils, triglyceride, and neutrophil-to-lymphocyte ratio levels and lower mean corpuscular volume level, compared with the control group (P = 0.002, P < 0.001, P = 0.003, P = 0.002, and P = 0.027, respectively). White blood cell, neutrophil, triglyceride, and neutrophil-to-lymphocyte ratio were independent risk factors for PCV (odds ratio [OR] = 1.668, 2.324, 2.846, and 2.543, respectively; P = 0.003, P = 0.001, P = 0.005, and P = 0.004, respectively). Mean corpuscular volume was an independent protective factor against PCV (OR = 0.902; P = 0.031). Receiver operating characteristic curve analysis revealed that the area under the curve values for white blood cell, neutrophil, triglyceride, neutrophil-to-lymphocyte ratio, and mean corpuscular volume was 0.656, 0.687, 0.660, 0.659, and 0.633, respectively (P< 0.05, respectively). The combined area under the curve value was 0.772 (P < 0.001). CONCLUSIONS: White blood cells, neutrophils, triglycerides, and the neutrophil-to-lymphocyte ratio were the risk factors for PCV. Mean corpuscular volume was a protective factor against PCV. These results suggested that the combination of white blood cells, neutrophils, triglyceride, neutrophil-to-lymphocyte ratio, and mean corpuscular volume can be used to predict PCV.

Insm1 promotes differentiation of retinal progenitor cells toward photoreceptor cells in the developing retina through up-regulation of SHH.

This article investigated the effect of Insm1 on RPC differentiation in mice and the underlying mechanism. The retinal tissues of mouse embryo at 12.5 days (E12.5) and postnatal 14 days (P14) were collected, following by the detection of Insm1 and corresponding markers by immunofluorescent staining. RPCs isolated from retinal tissues at P1 were cultured in culture medium for 7 days. The differentiation of photoreceptor and glial cells was assessed after RPCs transferred to the differentiation medium for 20 days. Next, the effect of Insm1 overexpression on the differentiation of RPCs toward rod photoreceptor and glial cells were assessed. Insm1 was highly expressed in RPCs of retinal tissues and decline in photoreceptor cells, while hardly expressed in glial cells. Based on the results of Pax-6 positive immunofluorescent staining and flow cytometry detection, RPCs were successfully isolated from retinal tissues. After the culture in differentiation medium, RPCs showed positive staining of Rhodopsin and glial fibrillary acidic protein (GFAP). Further results showed that overexpression of Insm1 significantly increased the percentage of Rhodopsin positive cells, and up-regulated Sonic Hedgehog (SHH), hairy and enhancer of split homolog-1(Hes1), S-opsin and Rhodopsin levels, while decreased the percentage of Glutamine synthetase positive cells, and reduced Glutamine synthetase and GFAP levels. Whereas, the effect of Insm1 overexpression on these protein levels were partly abolished by the knockdown of SHH or Hes1. We conclude that Insm1 promotes the differentiation of RPCs into photoreceptor cells in the developing retina through up-regulation of SHH.

Elevated neutrophil counts, triglycerides, monocyte/high-density lipoprotein (HDL) ratios, and lower HDL in patients with retinal vein occlusion.

Introduction Aim to evaluate associations of peripheral blood immune cells and blood lipid profile levels with retinal vein occlusion (RVO). Methods This retrospective study included 127 patients with RVO and 108 controls. Patients with RVO were divided into branch RVO (BRVO), central RVO (CRVO), ischemic RVO, or non-ischemic RVO groups. Medical records were collected and analyzed. Results The RVO group had higher mean neutrophil, triglyceride (TG), and monocyte/high-density lipoprotein (HDL) ratio (MHR) levels and lower HDL levels (P=0.037, P<0.001, P=0.004, and P=0.002, respectively). TG and MHR levels were significantly higher in the BRVO and CRVO groups compared with the control group (P<0.001, P=0.016, respectively), but there was no difference in BRVO and CRVO group (P=0.972, P=0.916, respectively). Mean HDL levels were significantly lower in the BRVO and CRVO groups than in the control group (P=0.005), but the difference between the BRVO group and CRVO group was not significant (P=0.290). Neutrophils, TG, and MHR were independent risk factors for RVO. HDL was an independent protective factor for RVO. Age was an independent risk factor for ischemic RVO. Conclusions Lower HDL, and higher neutrophil, TG and MHR levels are associated with RVO. Age is an independent risk factor for ischemic RVO.

Combined therapy guided by multimodal imaging of fifteen retinal capillary hemangioblastomas in a monocular Von Hippel- Lindau syndrome case report.

BACKGROUND: To report the multimodal imaging and treatment of fifteen retinal capillary hemangioblastomas (RCHs) associated with Von Hippel-Lindau syndrome in a monocular patient during a long-term following-up, which supply high-resolution exquisite SS-OCTA images (VG200; SVision Imaging, Ltd., Luoyang, China) and management experience about multiple RCHs. CASE PRESENTATION: A 34-year-old monocular male patient complained decreased visual acuity (20/100) without pain and redness in the left eye five years ago. Von Hippel-Lindau syndrome were diagnosed with genetic testing. He, his son and daughter all carried a heterozygosity missense variant c.499C > T (p. Arg167Trp) in the Hg19 gene, a VHL gene located in Chr3:10,191,506. Fifteen RCHs were identified by the application of multimodal imaging, which including fundus photo, fundus autofluorescence (FAF), B-scan ultrasonography (US), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) and swept-source optical coherence tomography angiography (SS-OCTA). Transscleral cryotherapy and laser photocoagulation were performed to destroy the largest RCH with the size of 4 PD in diameter. Laser photocoagulation was conducted to seal the middle or tiny RCHs (< 1.5 PD) and their nourishing vessels. The retinal edema and exudative macular detachment were successfully relieved by intraocular injection of bevacizumab for 5 times. The RCHs in the left eye responded well to these treatments and best corrected visual acuity was 20/25 for three years. Three-month recall visits were recommended for him. CONCLUSION: For multiple retinal capillary hemangioblastomas in monocular patients, precise combined therapy guided by multimodal imaging has a profound impact on the management of new and recurrent RCHs.

Association of miRNA-146a Gene Polymorphism Rs2910164 with Behcet's Disease: A Meta-analysis.

BACKGROUND: A meta-analysis was performed by summarizing relevant researches to evaluate the relationship between miRNA-146a gene polymorphism rs2910164 and Behcet's disease (BD). METHODS: A systematic search of published studies was conducted in PubMed and Embase. Five eligible studies involving 1167 BD cases and 1662 controls were included in the current meta-analysis. RESULTS: The results suggested that the polymorphism rs2910164 was correlated with BD susceptibility in all genetic models. In subgroup analysis according to ethnicity, the relationship between this polymorphism and BD was more significant in Caucasians (allele model: OR = 0.49, 95% CI 0.39-0.61; heterozygote model: OR = 0.35, 95% CI 0.26-0.47; homozygote model: OR = 0.29, 95% CI 0.16-0.53; dominant model: OR = 0.34, 95% CI 0.25-0.45; recessive model: OR = 0.56, 95% CI 0.50-0.72) than that in Asians. CONCLUSION: In conclusion, this meta-analysis indicates that miRNA-146a gene polymorphism rs2910164 G allele confers BD susceptibility, especially in Caucasians.

The Aflibercept-Induced MicroRNA Profile in the Vitreous of Proliferative Diabetic Retinopathy Patients Detected by Next-Generation Sequencing.

Purpose: Vascular endothelial growth factor-A (VEGF-A) is an important pathogenic factor in proliferative diabetic retinopathy (PDR), and aflibercept (Eylea) is one of the widely used anti-VEGF agents. This study investigated the microRNA (miRNA) profiles in the vitreous of 5 idiopathic macular hole patients (non-diabetic controls), 5 untreated PDR patients (no-treatment group), and 5 PDR patients treated with intravitreal aflibercept injection (treatment group). Methods: Next-generation sequencing was performed to determine the miRNA profiles. Deregulated miRNAs were validated with quantitative real-time PCR (qRT-PCR) in another cohort. The mRNA profile data (GSE160310) of PDR patients were retrieved from the Gene Expression Omnibus (GEO) database. The function of differentially expressed miRNAs and mRNAs was annotated by bioinformatic analysis and literature study. Results: Twenty-nine miRNAs were significantly dysregulated in the three groups, of which 19,984 target mRNAs were predicted. Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were validated to be remarkably upregulated in no-treatment group versus controls, and significantly downregulated in treatment group versus no-treatment group. In the GSE160310 profile, 204 deregulated protein-coding mRNAs were identified, and finally 179 overlapped mRNAs between the 19,984 target mRNAs and 204 deregulated mRNAs were included for further analysis. Function analysis provided several roles of aflibercept-induced miRNAs, promoting the alternation of drug sensitivity or resistance-related mRNAs, and regulating critical mRNAs involved in angiogenesis and retinal fibrosis. Conclusion: Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were highly expressed in PDR patients, and intravitreal aflibercept injection could reverse this alteration. Intravitreal aflibercept injection may involve in regulating cell sensitivity or resistance to drug, angiogenesis, and retinal fibrosis.

Relationship between elevated microRNAs and growth factors levels in the vitreous of patients with proliferative diabetic retinopathy.

AIM: The aim of this study was to identify differentially expressed microRNAs (miRNAs) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and correlate some of them with growth factors. METHODS: Vitreous samples were collected from 5 PDR eyes and 5 control eyes, and then miRNAs were assayed with next-generation sequencing (NGS). Three differentially expressed miRNAs were validated in vitreous of another cohort using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). RESULTS: Transforming growth factor ß (TGF-ß) and vascular endothelial growth factor (VEGF) signaling pathway were excavated out through bioinformatic analysis of deregulated miRNAs. The expression of hsa-miR-24-3p, hsa-miR-197-3p and hsa-miR-3184-3p, VEGF-A and TGF-ß were confirmed to be significantly higher in the vitreous of PDR eyes than controls(P < 0.05). Furthermore, Pearson's correlation analysis showed significantly positive correlations between these elevated miRNAs and growth factors (P < 0.05). CONCLUSIONS: Elevated vitreous levels of hsa-miR-24-3p, hsa-miR-197-3p, hsa-miR-3184-3p in PDR patients may play roles in pathophysiology of PDR, the target mRNAs of which significantly enriched in VEGF and TGF-ß signaling pathways. Positive correlations between elevated vitreous levels of the three miRNAs and VEGF-A, TGF-ß in PDR patients could provide a novel research direction for PDR.

Ferulic acid (FA) protects human retinal pigment epithelial cells from H2 O2 -induced oxidative injuries.

The aim of present study is to investigate whether Ferulic acid (FA), a natural polyphenol antioxidant, was able to protect ARPE-19 cells from hydrogen peroxide (H2 O2 )-induced damage, and elucidate the underlying mechanisms. Our results revealed that FA pre-treatment for 24 hours can reverse cell loss of H2 O2 -induced ARPE-19 cells via the promotion of cell proliferation and prevention of apoptosis, as evidenced by 5-ethynyl-2'-deoxyuridine (EdU) incorporation and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay, respectively. Moreover, the addition of FA (5 mM) can decrease Bax and cleaved caspase-3 protein expression, but increase Bcl-2 protein expression in ARPE-19 cells. Furthermore, H2 O2 -induced oxidative stress in ARPE-19 cells was significantly alleviated by FA, illustrated by reduced levels of ROS and MDA. In addition, the attenuated antioxidant enzymes activities of (SOD, CAT and GPX) and GSH level were reversed almost to the normal base level by the pre-addition of FA for 24 hours. In all assays, FA itself did not exert any effect on the change of the above parameters. These novel findings indicated that FA effectively protected human ARPE-19 cells from H2 O2 -induced oxidative damage through its pro-proliferation, anti-apoptosis and antioxidant activity, suggesting that FA has a therapeutic potential in the prevention and treatment of AMD.

Experimental Study of the Biological Properties of Human Embryonic Stem Cell-Derived Retinal Progenitor Cells.

Retinal degenerative diseases are among the leading causes of blindness worldwide, and cell replacement is considered as a promising therapeutic. However, the resources of seed cells are scarce. To further explore this type of therapy, we adopted a culture system that could harvest a substantial quantity of retinal progenitor cells (RPCs) from human embryonic stem cells (hESCs) within a relatively short period of time. Furthermore, we transplanted these RPCs into the subretinal spaces of Royal College of Surgeons (RCS) rats. We quantified the thickness of the treated rats' outer nuclear layers (ONLs) and explored the visual function via electroretinography (ERG). It was found that the differentiated cells expressed RPC markers and photoreceptor progenitor markers. The transplanted RPCs survived for at least 12 weeks, resulting in beneficial effects on the morphology of the host retina, and led to a significant improvement in the visual function of the treated animals. These therapeutic effects suggest that the hESCs-derived RPCs could delay degeneration of the retina and partially restore visual function.

Ranibizumab versus bevacizumab for the treatment of idiopathic choroidal neovascularization: 2-Year results.

PURPOSE: To compare the efficacy and safety of bevacizumab vs ranibizumab for the treatment of idiopathic choroidal neovascularization (ICNV). METHODS: This retrospective study included 60 eyes of 60 patients with ICNV who underwent intravitreal injection of bevacizumab (1.25 mg/0.05 mL, n = 30 eyes) or ranibizumab (0.5 mg/0.05 mL, n = 30 eyes). Multiple treatments were based on complete ophthalmologic investigation including slit-lamp biomicroscopy, fundus examination, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), and best-corrected visual acuity (BCVA). The BCVA, central retinal thickness (CRT), intraocular pressure (IOP), FFA results, and complications were compared between the 2 groups during the 2-year follow-up. RESULTS: Visual acuity was significantly better at 1, 3, 6, 12, and 24 months after treatment (p<0.01), with no significant difference in visual acuity between the bevacizumab and ranibizumab groups. In both groups of patients, the CRT after treatment was significantly less than before. At 12 and 24 months, the CRT in the ranibizumab group was significantly less than in the bevacizumab group (p<0.05). The FFA examination showed that CNV was reduced after intravitreal injection of either drug, with no significant difference in IOP between the 2 groups. No ophthalmologic or systemic complications occurred. CONCLUSIONS: Bevacizumab and ranibizumab are effective and safe in the treatment of ICNV, with similar effects in improving visual acuity and reducing retinal edema. The long-term efficacy of ranibizumab is superior to bevacizumab in reducing CRT.