BackgroundDiabetic retinopathy (DR) is deemed a microangiopathy and neurodegenerative disorder, which is a primary reason of visual impairment in the world. Ferritinophagy is a critical regulator of ferroptosis and has a vital part in the etiopathogenesis of DR. Nevertheless, its molecular mechanism in DR remains to be expounded.MethodsThe GSE146615 dataset was adopted to identify ferritinophagy-related differentially expressed genes (FRDEGs). The interactions and biological functions of the genes were described by means of functional enrichment analysis (FEA). The enriched gene sets were analyzed utilizing gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). Identification of hub genes was performed utilizing protein–protein interaction (PPI) analysis. mRNA–miRNA, mRNA–transcription factors (TF), mRNA–drugs, mRNA–RNA-binding proteins (RBP) interaction networks were constructed. In addition, datasets GSE60436 and GSE94019 were utilized for validation. The diagnostic performance of FRDEGs was assessed by means of receiver-operating characteristic curve monofactor analysis, followed by immune infiltration analysis. Lastly, quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to analyze the validation of genes.ResultsIn total, the identification of eight FRDEGs was completed utilizing differential expression analysis. FEA mainly implicated the autophagy of mitochondrion, mitochondrion disassembly, autophagosome assembly, and organization pathways. GSEA and GSVA mainly implicated the interferon alpha response, ultraviolet response up, interferon gamma response, apical junction, pical surface, and allograft rejection pathways. BECN1 and HERC2 displayed high diagnostic accuracies in validation sets. Immune infiltration analysis revealed that several immune cells related to ferritinophagy may be play potential roles in DR. Finally, qRT-PCR was utilized to validate the upregulated expression of BECN1 as well as the downregulated expression of BCAT2 and ATG7 in the DR model.ConclusionBECN1, HERC2, ATG7, and BCAT2 act as potential biomarkers for DR and might regulate ferritinophagy and the immune microenvironment to influence its development and progression. This research can provide new insights into pathogenesis of DR related to ferritinophagy.

Purpose: To observe the relationship between the characteristic changes in the drusen morphology revealed by the spectral-domain optical coherence tomography (SD-OCT) and the progression of age-related macular degeneration (AMD). Methods: A total of 380 drusen in 45 eyes in 35 patients with the intermediate drusen were longitudinally followed up every 6 months by SD-OCT for a period of 24 months. The drusen were divided into the dynamic group and stable group according to the following parameters: number, volume, concurrent retinal pigment epithelium (RPE)/ellipsoid zone (EZ) damage, and the development of advanced AMD. The morphological characteristics of the progressive or stable drusen were further analyzed. Odds ratios (ORs) and the risk for the drusen progression were calculated. Results: The level of interobserver and intraobserver agreement for each drusen tomographic morphological parameters ranged from 82.7 to 90%. At the end of an average follow-up of 15.92 ± 6.99 months, six patients developed choroidal neovascularization and no patients developed geographic atrophy. Finally, 139 drusen changed and 241 drusen remained stable. The drusen with low reflectivity ( p < 0.001; OR: 5.26; 95% CI: 2.24–12.36), non-homogeneity without a core ( p < 0.001; OR: 4.31; 95% CI: 2.08–8.92), RPE damage ( p < 0.001; OR: 28.12; 95% CI: 9.43–83.85), and the EZ damage ( p < 0.001; OR: 14.01; 95% CI: 5.28–37.18) were significantly associated with active change; the drusen with low reflectivity ( p = 0.01; OR: 2.95; 95% CI: 1.29–6.75) and decreased overlying RPE reflectivity ( p < 0.001; OR: 21.67; 95% CI: 9.20–51.02) were the independent predictors for progression. The drusen with high reflectivity were significantly associated with stabilization ( p = 0.03; OR: 0.17; 95% CI: 0.04–0.84). Conclusion: Spectral-domain optical coherence tomography is an optimized, accurate, and efficient method to follow-up the drusen. The intermediate non-exudative AMD prognosis of the patient was most strongly correlated with the drusen reflectivity and disruption of the overlying RPE layer. The drusen with low reflectivity and overlying RPE damage were more likely to progress and required frequent follow-up.

OBJECTIVE:To investigate the clinical effect of microsurgical scleral drainage and trabeculectomy combined with scleral flap adjustable suture technique in the treatment of primary glaucoma.METHODS:One hundred primary glaucoma patients (120 eyes) in Xinyu People's Hospital of Jiangxi province were selected from July 2014 to June 2016. The patients were randomly divided into control group and study group. The control group was treated with compound trabeculectomy, while the study group was treated with microsurgical scleral drainage and trabeculectomy combined with scleral flap adjustable suture technique. In both groups of patients, intraocular pressure, functional filtering bleb formation, and complications before and after surgery were monitored for three days, one week, one month, three months, six months and one year, while anterior chamber depth was determined one week after operation. The extent of success of operation was compared between the two groups.RESULTS:At three days, one week, one month, three months, six months and one year after surgery, intraocular pressure of study group was significantly lower than that of the control group (P<0.05). There was 93.33% formation of functional filtering blebs in the study group, which was significantly higher than that in the control group (60.00%, P<0.001). Moreover, normal anterior chamber formation was significantly higher in the study group (91.67%) than in the control group (71.67%, P<0.01). There was 95.00% operation success in the study group, relative to 68.33% success in the control group (P<0.001).CONCLUSION:Microsurgical scleral drainage and trabeculectomy combined with scleral flap adjustable suture technique has better curative effect on primary glaucoma than compound trabeculectomy. Moreover, it does not exacerbate complications. Therefore, the combination treatment technique merits clinical application.

Optical coherence tomography (OCT) is a valuable ancillary test in the diagnosis and management of chorioretinal disease. The evaluation of choroid thickness using OCT has become the focus of clinical applications. We report a linear artifact that acts as a confounding factor in choroidal thickness measurements by enhanced depth imaging OCT. We found that the linear artifact is located stably at a depth of 485 μm beneath the retinal pigment epithelium in 81.88% of subjects. The study suggested that the linear artifact was a confounding factor in assessing choroidal thickness and that caution should be used in the interpretation of the choroidal thickness, especially when it is approximately 485 μm.

Objective To analyze the symmetry of binocular phenotype in patients with age-related macular degeneration (AMD) and to investigate the risk factors.Methods In this retrospective study,141 AMD patients were recruited from 2012 to 2014 in Zhongshan ophthalmic center,Sun Yat-sen University.Patients were divided into 3 groups:bilateral drusen (Group A),drusen in one eye and exudative AMD in the other eye (Group B) and bilateral exudative AMD (Group C).Age,the distribution of gender,history of hypertension,smoking and overweight were recorded and compared among 3 groups.Results In all 141 patients,124 were with bilateral AMD (87.9％) and 17 were with unilateral AMD (12.1％).Symmetry of binocular phenotype was found in 72 patients (51.1％),among them bilateral drusen,bilateral exudative AMD and bilateral geographic atrophy (GA) was found in 42 patients (29.8％),22 patients (15.6％) and 8 patients (5.7％) respectively.In 52 patients (36.8％),phenotype was inconsistent between the two eyes.Among the patients with unilateral drusen,46 patients (32.6％) were with exudative AMD and 3 patients (2.1％) were with GA in the fellow eye.Three patients (2.1％) were with GA in one eye and exudative AMD in the fellow eye.The proportion of age and history of smoking were statistically different in Group A,B,and C (all P ＜0.05).The differences of age between group A and C,B and C were statistically significant (P =0.006 and 0.044).There were more smoking patients in group C than in group A (P =0.019).Conclusions More than half of AMD patients have symmetrical fundus phenotype.The most common type of bilateral AMD phenotype is drusen in one eye and exudative AMD in the fellow eye.Aging and smoking unilateral exudative AMD patients need close follow-up in case of severe visual impairment in the fellow eye.

MicroRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory function, playing crucial roles in cancer development and progression of human melanoma. Previous studies have indicated that miR-769 was implicated in diverse biological processes. However, the underlying mechanism of miR-769 in human melanoma has not been intensively investigated. In this present study, we aimed to investigate the role of miR-769 and its target genes in human melanoma. We found that miR-769 expression was strongly increased in human melanoma cells and clinical tissues compared with their corresponding controls. Overexpression of miR-769 promoted cell proliferation in human melanoma cell line A375, whereas miR-769-in reverses the function. Glycogen synthase kinase-3 Beta (GSK3B), a potential target gene of miR-769, and was validated by luciferase assay. Further studies revealed that miR-769 regulated cell proliferation of human melanoma by directly suppressing GSK3B expression and the knockdown of GSK3B expression reversed the effect of miR-769-in on human melanoma cell proliferation. In summary, our data demonstrated that miR-769 might act as a tumor promoter by targeting GSK3B during development of human melanoma.

To evaluate the changes of the photoreceptor layer (PRL) thickness with spectral domain optical coherence tomography (SD-OCT) and the retinal function by mfERG, as well as the correlation of morphology and function parameters in subjects with early and intermediate age-related macular degeneration (AMD).

Objective To observe the morphologic characteristics of drusen in atrophic age-related macular degeneration (AMD) by spectral domain optical coherence tomography (SD-OCT).Methods Fifty-four patients (84 eyes) with macular drusen and atrophic AMD,and 56 age-matched control patients (56 eyes) with cataract were included in this study.Atrophic AMD patients were divided into two groups:D1 group with drusen involving the fovea (42 eyes) and D2 group with drusen not involving the fovea (42 eyes).The SD-OCT images in macular (6 mm× 6 mm scans) were acquired,and the foveal retinal thickness (FRT) was measured.The size,morphology,inner reflection,homogeneity of drusen and its relationship with surrounding tissues were analyzed.Results The FRT of D1 group,D2 group and control group were (160.90±38.47),(194.21±26.11),(222.42± 19.29) μm respectively.The FRT of D1 group and D2 group were thinner than that of control group (F=57.08,P=0.00).Totally 1124 drusen were found by SD-OCT images in 84 eyes,with an average of 10.84 drusen in each eye.3.0％,12.5％ and 84.5％ of all 1124 drusen were small,medium and large sized respectively.56.6％,14.2％,20.4％ and 8.8％ of all drusen were dome,pointed,saw-toothed and basal-shaped respectively.17.1 ％,57.5％ and 25.4％ of all drusen had low,medium and high internal reflectivity respectively.The internal reflectivity of 65.6％,2.8％ and 31.7％ of all drusen were homogeneous,nonhomogeneous with core,and nonhomogeneous without core respectively.Overlying retinal pigment epithelium (RPE) damage and photoreceptor inner segment/outer segment (IS/OS) junction damage were presented in 34.5 ％ and 24.8 ％ drusen respectively.The most common type of drusen was dome-shape,homogeneous,with medium internal reflectivity,and without overlying RPE or IS/OS junction damage (81.0％).Conclusions The FRT becomes thinner in patients with drusen.The most common drusen types are dome-shaped,homogeneous,with medium internal reflectivity,and without overlying RPE or IS/OS junction damage.

Objective To evaluate the repeatability and reproducibility of macular ganglion cell-inner plexiform layer (GCIPL) thickness measurement using spectral-domain optical coherence tomography (Cirrus HD-OCT).Method One hundred and eight eyes of 54 normal subjects (26 males and 28 females) between 19 and 75 years of age [mean age (46.2± 16.5) years] were included.Each eye underwent macular scanning using Cirrus HD-OCT Macular Cube 512 × 128 protocol by two operators.Three scans of each eye were obtained by each operator.For the right eye of each subject,three extra scans were obtained using Macular Cube 200 × 200 protocol by one operator.The average,minimum,superotemporal,superior,superonasal,inferonasal,inferior,and inferotemporal GCIPL thickness was analyzed and the repeatability of GCIPL thickness measurement was evaluated with intra-operator,inter-operator,intra-protocol,and inter-protocol intraclass correlation coefficients (ICC).Ten extra scans were obtained from the left eyes of 10 randomly selected subjects for reproducibility assessment with coefficients of variation (CV).Results The intra-operator ICC of macular GCIPL measurement using Macular Cube 512 × 128 protocol by two operators were 0.959-0.995 and 0.954-0.997,respectively; and the inter-operator ICC were 0.944-0.993.All intra-and inter operator ICC were ＞0.800 with the highest and lowest records of the average and minimum GCIPL thickness,respectively.The intra-protocol ICC of Macular Cube 512 × 128 protocol and Macular Cube 200× 200 protocol were 0.986-0.996 and 0.927-0.997,respectively; and the inter-protocol ICC were 0.966 0.994.All intra-and inter-protocol ICC were ＞0.800.CV of GCIPL thickness measurement using MacularCube 512×128 protocol were (0.70±0.31)％ (1.35±0.86)％.Conclusion Cirrus HDOCT can measure macular GCIPL thickness in normal eyes with excellent repeatability and reproducibility.

Background Reducing ocular surface toxicity induced by topical antiglaucoma medications,and thus improving the therapeutic compliance of glaucomatous patients to treating drug become an urgent issue in the long-term antiglaucomatous therapies.Whether polyethylene glycol,a new type of artificial tear,can play a protective role from ocular surface toxicity induced by topical antiglaucoma medications remains further study.Objective The present study was to investigate the protective effect of polyethylene glycol on ocular surface toxicity induced by prolonged use of benzalkonium chloride-preserved latanoprost eye drops.Methods Thirty adult female New Zealand rabbits were randomly divided into normal control group,phosphate buffer solution (PBS) group and polyethylene glycol eye drops group.PBS with 0.005％ latanoprost was topically administered for consequent 60 days in the PBS group,and 0.005％ latanoprost with polyethylene glycol eye drops was used at the same way in the polyethylene glycol group.Schirmer Ⅰ test,fluorescein and rose bengal staining of cornea and conjunctiva,conjunctiva impression cytology specimens collecting were performed before experiment as well as 31 and 61 days after administration of drug.Histomorphological and ultrastructural changes of cornea and conjunctiva were observed under the light microscopy,scanning and transmission electron microscopy on day 61.Results The score of corneal fluorescine staining was significantly different among the control group,PBS group and polyethylene glycol group (H =25.265,P＜0.001 ;H=29.426,P＜0.001) on day 31 and day 61.Significant difference also was found in the score of rose bengal staining of cornea and conjunctiva (H=26.167,P＜0.001 ;H =29.212,P＜0.001),Schirmer Ⅰ test value (F=4.746,P＜0.05) and conjunctival goblet cell density (F=18.055,P＜0.001).Compared with the control group,corneal fluorescein scores [0(0,1.0) vs.3 (2.0,3.0)] and rose bengal scores [0(0,1) vs.2(2,3)] were significantly increased (both P＜0.001),and Schirmer Ⅰ test value scores and conjunctival goblet cell density were decreased ((5.18±0.46/)mm vs.(9.43±0.57)mm;(53.04±2.98)/HP vs.(87.73±2.34)/HP) (both P＜0.01)on day 61.Impaired microvilli and organelles of the corneal and conjunctival epithelial cells were observed.Compared with PBS-treated group,PEG-treated group showed decrease in fluorescein [3(2.0,3.0) vs.1 (0.5,1.0)] and rose bengal scores [2 (2,3) vs.1 (0,1)] (both P＜0.001),increase in Schirmer Ⅰ test value scores [(7.00±0.71)mm vs.(5.18±0.46) mm,P＜0.05],increase in goblet cell density ((63.88±3.32)/HP vs.(53.04±2.98)/HP,P＜0.05) and improvement of grading scores of conjunctival epithelium on day 61.In addition,complete mierovilli and cell organelles were found in the corneal and conjunctival epithelial cells in the polyethylene glycol group.Conclusions Topical application of polyethylene glycol can decrease the ocular surface toxicity induced by benzalkonium chloride-preserved latanoprost.

PURPOSE To investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by benzalkonium chloride (BAC)-preserved latanoprost. METHODS Twenty-one white rabbits (42 eyes) were randomly divided into three groups. The control group was untreated. The two experimental groups were treated with 0.02% BAC-containing latanoprost once a day combined with unpreserved 0.3% SH or PBS three times daily for 60 days. Schirmer test, fluorescein and rose bengal staining, and conjunctiva impression cytology were performed on days 0, 31, and 61. Apoptosis of conjunctival epithelium was detected by TUNEL assay on day 61. Conjunctival inflammation was evaluated with light microscopy. Cornea and conjunctiva ultrastructure were observed by electron microscopy. RESULTS Compared with the control group, the PBS-treated latanoprost group showed increases in fluorescein and rose bengal scores, decreases in Schirmer scores, and goblet cell density (GCD) on days 31 and 61. Increases in inflammatory and apoptotic cells in conjunctiva, and ultrastructural disorders of the cornea and conjunctiva were also observed on day 61. Compared with the PBS-treated latanoprost group, the SH-treated latanoprost group showed decreases in fluorescein and rose bengal scores, and increases in Schirmer scores and GCD on days 31 and 61. Decreases in inflammatory and apoptotic cells in conjunctiva and amelioration of ultrastructural disorders were also observed. CONCLUSIONS Topical application of SH significantly decreased the ocular surface toxicity induced by BAC-preserved latanoprost. As a vehicle or neutralizing material, SH could be proposed to reduce ocular toxicity and protect the ocular surface in long-term BAK-preserved antiglaucoma medication treatment.