Comparison of anterior sclera thickness in emmetropes and myopes.

BACKGROUND: This study aimed to compare anterior scleral thicknesses (ASTs) in people with emmetropia and myopia to explore the effect of myopia on AST. METHODS: In this cross-sectional study, 93 participants (i.e., 93 eyes) with emmetropia and myopia underwent ocular imaging via anterior segment optical coherence tomography. We acquired raw B-scan OCT images along each of the four meridians (superior, inferior, nasal, and temporal), The AST was estimated from the limbus to a distance of 6 mm. The participants were aged between 20 and 50 years (mean age: 30.2 ± 8.8 years). The axial length (AL) was 22.50 ~ 33.04 mm (mean AL: 26.51 ± 2.65 mm), and the spherical equivalent (SE) was + 0.50 ~ 27.5 D (mean SE: -7.20 ± 6.5 D). The selected sample comprised 37 males and 56 females who were categorized as emmetropes, mild-moderate myopes, or high myopes. The four meridians of AST, AL, and refractive error were observed. RESULTS: The AL was significantly negatively correlated with the four meridians of AST (the r value ranged between - 0.511 and - 0.228, P < 0.05). There was no significant correlation between age and inferior diameter (r = 0.113, P = 0.314), but age was positively correlated with the average AST of the superior, temporal, and nasal diameters (the r value ranged between 0.452 and 0.552, P < 0.05). There was no significant correlation between sex and AST (the T value ranged between - 1.816 and - 0.130, P > 0.05). Except for the inferior diameters of 1 mm, 5 mm, and 6 mm and the temporal diameter of 1 mm, the four diameters in the emmetropia group and the high myopia group were statistically significant at a distance of 0 ~ 6 mm from the limbus (P < 0.05). CONCLUSION: The AST is negatively correlated with AL and positively correlated with age. Compared with emmetropic eyes, the AST is thinner in highly myopic eyes. Myopia affects AST, which may be useful for monitoring progression in cases of myopia.

Sirtuin (Sirt) 3 Overexpression Prevents Retinopathy in Streptozotocin-Induced Diabetic Rats.

BACKGROUND Sirtuin (Sirt) 3 could promote autophagy by downregulating the expression of genes related to neovascularization in retinal endothelial cells. In this study, we aimed to investigate the effect of Sirt3 overexpression on retinopathy in streptozotocin (STZ)-induced diabetic rats, and to assess its mechanisms. MATERIAL AND METHODS Ntraperitoneal injection of STZ in rats was used to produce a diabetic model. The study rats were divided into 4 groups (n=6 for each group): a control group; a model group; a model+scrambled adenovirus group; and a model+Sirt3 overexpression group. Hematoxylin and eosin (H&E) staining determined the pathological changes of retina tissues. Immunohistochemistry, fluorescence quantitative polymerase chain reaction, and western blotting were used to detect the expression of Sirt3, vascular endothelial growth factor (VEGF), and microtubule-associated protein 1A/1B-light chain 3 (LC3). RESULTS In the model group, the inner limiting membrane was swollen, uneven and thickened, and the capillary endothelial cells occasionally protruded into the inner limiting membrane. These abnormalities were prevented by Sirt3 overexpression. Compared with the control group, the expression of Sirt3 at both mRNA and protein levels in the model group was significantly reduced, while the expression of VEGF was increased versus the control group (P.

A study of dry eye after cataract surgery in MGD patients.

OBJECTIVE: To investigate the dry eye symptoms after cataract surgery in MGD patients and their relationships METHODS: The study included 115 patients (115 eyes) with age-related cataract that underwent uncomplicated cataract surgery, and the patients were divided into two groups according to the MGD diagnostic criteria: group A (MGD group) and group B (control group). Schirmer I test (ST-I), tear breakup time (TBUT), and corneal fluorescein staining (CFS) were performed preoperatively and at 3 days, 7 days, 14 days, and 30 days postoperatively. We also measured eyelid meibomian gland morphology, meibomian gland expression, and meibum character scores before and after the cataract surgery. RESULTS: Postoperatively, in group A, TBUT decreased and CFS scores increased significantly. ST-I increased in the early postoperative course but decreased later. The eyelid margin morphology scores and meibomian gland expression scores of group A significantly increased after the cataract operation. Thus, patients with MGD may have a greater chance of developing the dry eye disease after cataract surgery. Cataract surgery may aggravate the signs of MGD, and the severity of MGD may positively correlate with TBUT, CFS, and corneal lesions after surgery. CONCLUSIONS: The characteristics of dry eye after cataract surgery in patients with MGD are different from common cataract patients, changes in the early postoperative phase to the ocular surface were caused by surgical factors, and the damages to epithelial function in the later postoperative phase were mainly associated with the inflammation of the meibomian gland and eyelid.

GEP100/ARF6 regulates VEGFR2 signaling to facilitate high-glucose-induced epithelial-mesenchymal transition and cell permeability in retinal pigment epithelial cells.

Cell permeability and epithelial-mesenchymal transition (EMT) were found to be enhanced in diabetic retinopathy, and the aim of this study was to investigate the underlying mechanism. ARPE-19 cell line or primary retinal pigment epithelial (RPE) cells were cultured under high or normal glucose conditions. Specific shRNAs were employed to knock down ADP-ribosylation factor 6 (ARF6), GEP100, or VEGF receptor 2 (VEGFR2) in ARPE-19 or primary RPE cells. Cell migration ability was measured using Transwell assay. Western blotting was used to measure indicated protein levels. RPE cells treated with high glucose showed increased cell migration, paracellular permeability, EMT, and expression of VEGF. Knockdown of VEGFR2 inhibited the high-glucose-induced effects on RPE cells via inactivation of ARF6 and MAPK pathways. Knockdown ARF6 or GEP100 led to inhibition of high-glucose-induced effects via inactivation of VEGFR2 pathway. Knockdown of ARF6, but not GEP100, decreased high-glucose-induced internalization of VEGFR2. High-glucose enhances EMT and cell permeability of RPE cells through activation of VEGFR2 and ARF6/GEP100 pathways, which form a positive feedback loop to maximize the activation of VEGF/VEGFR2 signaling.

Potential suppression of the high glucose and insulin-induced retinal neovascularization by Sirtuin 3 in the human retinal endothelial cells.

Retinal neovascularization generally play roles in the formation of various severe eye diseases, such as age-related macular degeneration and diabetic retinopathy. The regulation of neovascularization-related pathways by Sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, give us a cue that Sirt3 may participate in the retinal neovascularization. However, the mechanism remains unclear. Here, we established a retinal neovascularization model by using human retinal endothelial cells (HRECs) under the induction of high glucose and insulin (HGI). With this model, Sirt3-expressing lentivirus was constructed and then used to investigate the effect of Sirt3 overexpression on the expression of migration-, neovascularization- and autophagy-related genes. After the treatment of HGI on HRECs, the mRNA and protein levels of migration-related genes, including matrix metalloproteinase-2 (MMP-2) and MMP-9, were significantly upregulated. Meanwhile, angiogenesis-related genes, including vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α), and insulin-like growth factor-1 (IGF-1) were promoted at both mRNA and protein levels. However, HGI had no clear effect on the mRNA and protein levels of microtubule associated protein 1 light chain 3 (LC3), an autophagy-related gene. When Sirt3 was overexpressed by lentivirus infection after HGI, the upregulation of MMP-2, MMP-9, VEGF, HIF-1α, and IGF-1 were suppressed at both transcription and translation levels. At the same time, LC3 mRNA and LC3-II protein increased. These results suggest that Sirt3 may inhibit retinal neovascularization by regulating the migration-, neovascularization- and autophagy-related factors expression. Thus we argue that Sirt3 may be a potential candidate drug for curing various eye diseases induced by retinal neovascularization.

The effect of intraocular lens and lens eye on the treatment of macular splits in high myopia.

BACKGROUND: Macular retinoschisis in patients with high myopia is one of the main reasons for a decline in visual function and the perceived deformation of visual objects. OBJECTIVE: This study aimed to investigate the therapeutic effect of cataract phacoemulsification and foldable intraocular lens implantation (FILI) combined with internal limiting membrane stripping (ILMS) in the treatment of macular retinoschisis in patients with high myopia. METHODS: A total of 52 patients (55 eyes) who had been diagnosed with macular retinoschisis with high myopia between June 2019 and June 2020 were enrolled in the present study. Patients in the control group (25 eyes) received 23G vitreous surgery and macular ILMS and long-term inert gas (C3F8) filling of the vitreous cavity; patients in the research group (30 eyes) were additionally treated with cataract phacoemulsification and soft intraocular lens on the same treatment basis as the control group. RESULTS: The difference in average BCVA between the control and the research groups was not statistically significant before the surgery (P> 0.05) but was statistically significant 12 months after the procedure (P< 0.05). The minimum foveal thickness was significantly decreased in the two groups after the surgery compared with before the procedure (P< 0.05). CONCLUSION: Cataract phacoemulsification and FILI further improved the therapeutic effect of ILMS in the treatment of macular retinoschisis in patients with high myopia.

[Effects of External Carbon Sources on Ultimate Nitrogen Removal Performance and Microbial Community in Secondary Effluent Treating Process].

Adding external carbon sources is an important method for advanced nitrogen removal of secondary effluent in wastewater treatment plants (WWTPs). In order to compare the denitrification performance and economy of different carbon sources sufficiently, as well as the effect of long-term addition of carbon sources on the microbial population structure, four single carbon sources (methanol, ethanol, glucose, and sodium acetate) and four types of composite carbon sources were prepared by mixing sodium acetate and ethanol with a higher reaction rate and cheap glucose. The results showed that the effluent ρ(NOx--N) concentration of all systems was less than 1.0 mg·L-1 during the experiment. For single-carbon source systems, ethanol had the fastest denitrification rate, followed by sodium acetate and methanol; that of the glucose was the slowest. In the composite carbon source systems, the sodium acetate/glucose (1:1) with COD/ρ(N) was 6, which was equivalent to the results of sodium acetate/glucose (1:3), ethanol/glucose(1:1), and ethanol/glucose (1:3) with COD/ρ(N) of 9, 10, and 10, respectively. The sodium acetate/glucose (1:1) system had the fastest reaction rate and the best economy. High-throughput sequencing results showed that after more than 70 days of operation, the structure of the microbial community had changed completely. In the glucose-related system, the abundance of Candidatus Saccharibacteria, which is not popular in typical nitrogen removal systems, increased from 1.16% of seed sludge to 47.37%, and Saccharibacteria_genera_incertae_sedis correspondingly became the dominant community. This study not only provides a more comprehensive comparison for the selection of carbon sources in WWTPs with ultimate nitrogen removal but also provides basic data for the role of carbon sources in the domestication of microbial communities.

Intraoperative Optical Coherence Tomography in Idiopathic Macular Epiretinal Membrane Surgery.

Objective: To evaluate the feasibility and practicability of intraoperative optical coherence tomography (IOCT) in the surgery of idiopathic macular epiretinal membrane (IMM) without internal limiting membrane staining in all patients. Methods: Patients were selected from July 2018 to June 2020, and 32 patients (32 eyes) with IMM were operated with the use of IOCT. All patients underwent standard 23g vitrectomy. The internal limiting membrane was peeled off if there were obvious retinal folds. Intraoperative and postoperative complications, macular microstructural changes, and integrity of the detached membranes were recorded. The preoperative and postoperative best corrected visual acuity were compared. Results: The macular epiretinal membrane was completely removed in 75% (24 eyes) patients without internal limiting membrane staining, and in 15.6% (5 eyes) patients with combined internal limiting membrane stripping. The "starting point" of macular epiretinal membrane stripping was found in 75% (24 eyes), and the time required to find the best starting point ranged from 28s to 140s (mean 66 ± 15s). At 3 months after operation, 96.8% of the patients had stable or improved BCVA (p < 0.05). The central macular thickness of the affected eyes decreased significantly at 1 and 3 months after operation (p < 0.05). Conclusion: IOCT can significantly reduce the use of internal limiting membrane staining in idiopathic macular epiretinal membrane surgery, and it is safe, feasible and practical in idiopathic macular epiretinal membrane surgery without internal limiting membrane staining in all patients.

Intravitreal dexamethasone implant - a new treatment for idiopathic posterior scleritis: A case report.

BACKGROUND: Posterior scleritis is one of the most easily missed and misdiagnosed diseases in ophthalmology. In this case we treated a patient with intravitreal dexamethasone implant that has not been extensively studied before. CASE SUMMARY: A 40-year-old female patient who had anxiety, palpitation, and insomnia presented with eye pain and decreased vision in the left eye. An eye examination indicated that her visual acuity (VA) was 40/100. Her left eye presented conjunctival edema, mild exophthalmos, clear cornea, KP(-), and clear aqueous humor. In the fundus, there was a cinerous retinal protuberance. Ultrasonography showed "T-sign" and no systemic association was detected in laboratory examination. One month after injection of dexamethasone implant, the patient exhibited VA of 20/20, fundus serous retinal detachment disappeared, and intraocular pressure of both eyes was at the normal level. CONCLUSION: Intravitreal injection of dexamethasone implant may be a safe and effective treatment for patients with idiopathic posterior scleritis.

Targeting long non-coding RNA MALAT1 alleviates retinal neurodegeneration in diabetic mice.

AIM: To observe the effect of inhibiting long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on diabetic neurodegeneration. METHODS: Thirty-six 8-week-old C57BL/6 mice were randomly divided into normal control, diabetic control, diabetic scrambled small interfering RNAs (siRNAs) and diabetic MALAT1-siRNA groups. After diabetic induction with streptozocin intraperitoneally-injection, the diabetic MALAT1-siRNA group was intravitreally injected with 1 µL 20 µmol/L MALAT1 siRNA, and the diabetic scrambled siRNA group was injected with the same amount of scrambled siRNA. Electroretinography was performed to examine photoreceptor functions 16wk after diabetes induction. MALAT1 expression was detected via real time polymerase chain reaction. Cone morphological changes were examined using immunofluorescence. Rod morphological changes were examined by determining outer nuclear layer (ONL) thickness. RESULTS: The upregulation of retinal MALAT1 expression was detected in the diabetic control mice, while MALAT1 expression in the diabetic MALAT1-siRNA mice was decreased by 91.48% compared to diabetic control mice. The diabetic MALAT1-siRNA and diabetic control mice showed lower a-wave and b-wave amplitudes than did the normal control mice in scotopic and photopic electroretinogram, while the diabetic MALAT1-siRNA mice showed higher amplitudes than diabetic control mice. Morphological examination revealed that ONL thickness in the diabetic MALAT1-siRNA and diabetic control mice was lower than normal control mice. However, ONL thickness was greater in the diabetic MALAT1-siRNA mice than diabetic control mice. Moreover, the diabetic control mice performed a sparser cone cell arrangement and shorter outer segment morphology than diabetic MALAT1-siRNA mice. CONCLUSION: Inhibiting retinal MALAT1 results in mitigative effects on the retinal photoreceptors, thus alleviating diabetic neurodegeneration.

TRIM59 Promotes Retinoblastoma Progression by Activating the p38-MAPK Signaling Pathway.

Purpose: Retinoblastoma is a malignant tumor of the developing retina that mostly occurs in children. Our study aimed to investigate the effect of tripartite motif-containing protein 59 (TRIM59) on retinoblastoma growth and the underlying mechanisms. Methods: We performed bioinformatic analysis of three datasets (GSE24673, GSE97508, and GSE110811) from the Gene Expression Omnibus database. Quantitative reverse-transcription PCR and immunoblotting of three retinoblastoma cell lines were conducted to verify TRIM59 as a differentially expressed gene. Specific siRNAs were used to inhibit TRIM59 expression in the HXO-Rb44 cell line. A lentiviral vector was transfected into the Y79 cell line to overexpress TRIM59. The effects of TRIM59 on retinoblastoma cell proliferation, cell cycling, and apoptosis were explored in vitro using the abovementioned cell lines. The effect of TRIM59 expression on retinoblastoma cell proliferation was evaluated in a mouse xenograft tumor model. Results: TRIM59 expression in three retinoblastoma cell lines was remarkably elevated compared with normal control. Knocking down TRIM59 expression remarkably suppressed cell proliferation and growth and promoted cell apoptosis in HXO-Rb44 cells, whereas TRIM59 overexpression promoted tumor progression in Y79 cells. Silencing TRIM59 also markedly inhibited in vivo tumor growth in the xenograft model. Mechanistic studies revealed that TRIM59 upregulated phosphorylated p38, p-JNK1/2, p-ERK1/2, and p-c-JUN expression in retinoblastoma cells. Notably, the p38 inhibitor SB203580 attenuated the effects of TRIM59 on cell proliferation, apoptosis, and the G1/S phase transition. Conclusions: TRIM59 plays an oncogenic role in retinoblastoma and exerts its tumor-promotive function by activating the p38-mitogen-activated protein kinase pathway.

Progranulin protects the mouse retina under hypoxic conditions via inhibition of the Toll­like receptor­4­NADPH oxidase 4 signaling pathway.

To investigate the function of progranulin on the retina under hypoxic conditions, 8­week­old C57BL/6 mice were divided into normal condition and hypoxic condition groups (n=24 mice/group). The hypoxia model was established through intravitreal injection of 9 mM cobalt chloride. Subsequently, 10 mM progranulin and an equal amount of PBS were injected into the right and left eyes, respectively. Photoreceptor function was examined using electroretinogram (ERG) analysis. Morphological alterations were examined using immunofluorescence co­localization, retinal vascular inflammation was examined using the leukostasis assay, and signaling pathways were screened using immunoblotting. The results revealed that ERG amplitude was significantly lower under hypoxic conditions compared with under normal conditions. Furthermore, the amplitude was significantly reduced in the PBS­injected eyes compared with in the progranulin­injected eyes. Morphological examination demonstrated that the number of rods in the PBS­injected eyes was decreased compared with in the progranulin­injected eyes under hypoxic conditions. In addition, the arrangement of the cones was sparse and the morphology of the outer segments was short and small. Although the number of adherent leukocytes in the progranulin­injected eyes was higher in the hypoxic mice compared with in those under normal conditions, the number was only 52.31% of the number detected in the PBS­injected eyes. Analysis of the signaling pathways demonstrated that the protective effects of progranulin on retinas under hypoxic conditions were regulated by the Toll­like receptor 4 (TLR4)­NADPH oxidase 4 (NOX4) pathway, instead of the caspase and Wnt/ß­catenin pathways. In conclusion, progranulin exerted protective effects on the function and morphology of photoreceptors in a hypoxic environment, and could reduce retinal vascular inflammation, through inhibition of the TLR4­NOX4 pathway.

Forskolin attenuates retinal inflammation in diabetic mice.

The present study aimed to investigate the effect of forskolin on retinal inflammation under diabetic conditions. C57BL/6 mice were randomly divided into normal control, diabetic control and forskolin treatment groups. The diabetic model was established by intraperitoneal injection of streptozotocin. The forskolin treatment group received intragastrical administration of forskolin for 12 weeks, the other two groups received an equal amount of PBS. At 21 weeks following diabetic induction, an immunoblotting test was conducted to investigate the expression of two inflammatory factors: Intercellular adhesion molecule-1 (ICAM­1) and tumor necrosis factor­α (TNF­α). Glucose concentration was additionally calculated. A leukostasis assay was utilized to compare microvasculature pathological alterations. It was demonstrated that retinal glucose concentration of diabetic control and forskolin treatment were both increased compared with normal control, however the forskolin treatment group was only ~68.06% of the diabetic control due to downregulated glucose transporter 1 expression. The expression of ICAM­1 and TNF­α were upregulated in the forskolin treatment and diabetic control groups compared with the normal control, however these two inflammatory factor expression levels in the forskolin treatment group were ~68.75 and 75.37% of diabetic control. It was additionally observed that there were less adherent leukocytes in retinal microvasculature in the forskolin treatment group compared with diabetic control. All the differences observed were significant. Overall, by means of limiting glucose transport into the retina via forskolin, the retinal environment with lower glucose concentration alleviates the inflammatory response under diabetic conditions.

Homocysteine induces oxidative stress to damage trabecular meshwork cells.

The aim of the present study was to investigate the effect of homocysteine (Hcy) in on human trabecular meshwork cells (HTMCs). A total of 41 patients with primary open-angle glaucoma (POAG) and 53 patients with senile cataracts (control group) were recruited. Plasma and aqueous humor samples were collected and the Hcy concentrations were determined using enzymatic cycling assays. In cell experiments, normal HTMCs were passaged and randomly divided into a blank control group, a normal HTMC group and experimental groups, which were treated with different concentrations of Hcy. The HTMC activities were detected using the Cell Counting Kit-8 method and the HTMC mitochondrial membrane potential (MMP) was detected using JC-1 staining. Reactive oxygen species (ROS) released by trabecular meshwork cells was detected using flow cytometry and superoxide dismjutase-1 (SOD1) expression was detected using immunoblotting. The results revealed that the concentration of Hcy in the plasma and aqueous humor of the POAG group (14.44±0.86 and 1.60±0.27 µmol/l, respectively) was significantly higher compared with the control group (10.82±0.29 and 0.69±0.39 µmol/l). All tested concentrations (30, 100, 300 and 1,000 µmol/l) of Hcy reduced the MMP in HTMCs and inhibited HTMC proliferation in a dose-dependent manner. ROS production by HTMCs significantly increased with increased concentrations of Hcy, whereas SOD1 expression significantly decreased in a dose-dependent manner. In summary, patients with POAG were demonstrated to have increased concentrations of Hcy in the plasma and aqueous humor. High concentrations of Hcy in HTMCs induced an oxidative stress state, thereby further inhibiting HTMC proliferation. The results of the present study demonstrate that Hcy may be a potential treatment target in patients with POAG.

Bioinformatics Analysis of Weighted Genes in Diabetic Retinopathy.

Purpose: Intricate signaling networks and transcriptional regulators translate pathogen recognition into defense responses. The aim of this study was to identify the weighted genes involved in diabetic retinopathy (DR) in different rodent models of diabetes. Methods: We performed a gene coexpression analysis of publicly available microarray data, namely, the GSE19122 dataset from the Gene Expression Omnibus database. We conducted gene coexpression analysis on the microarray data to identify modules of functionally related coexpressed genes that are differentially expressed in different rodent models. We leveraged a richly curated expression dataset and used weighted gene coexpression network analysis to construct an undirected network. We screened 30 genes in the most closely related module. A protein-protein interaction network was constructed for the genes in the most related module using the Search Tool for the Retrieval of Interacting Genes. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for the 30 genes. Results: Five visual perception-related genes (Pde6g, Guca1a, Rho, Sag, and Prph2) were significantly upregulated. Based on the competing endogenous RNA hypothesis, a link between the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and visual perception-related mRNAs was constructed using bioinformatics tools. Six potential microRNAs (miR-155-5p, miR-1a-3p, miR-122-5p, miR-223-3p, miR-125b-5p, and miR-124-3p) were also screened. Conclusions: MALAT1 might play important roles in DR by regulating Sag and Guca1a through miR-124-3p and regulating Pde6g through miR-125b-5p.

Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from high glucose-induced apoptosis.

PURPOSE: Diabetic retinopathy (DR) is a major vision threatening disease mainly induced by high glucose. Despite great efforts were made to explore the etiology of DR, the exact mechanism responsible for its pathogenesis remains elusive. METHODS: In our study, we constructed diabetic rats via Streptozotocin (STZ) injection. TUNEL assay was employed to examine retinal cell apoptosis. The levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed via flow cytometry. The mRNA and protein levels of mitochondrial respiratory chain were investigated by RT-qPCR and western blot. RESULTS: Compared with normal rats, the retinal cell apoptosis rate in diabetic rats was significantly upregulated. What's more, the signals of 8-OHdG and the levels of Cytochrome C in diabetic rats were enhanced; however, the MnSOD signals and NADPH-1 levels were reduced. We investigated the effect of mitochondrialy targeted hOGG1 (MTS-hOGG1) on the primary rRECs under high glucose. Compared with vector-transfected cells, MTS-hOGG1-expressing cells blocked high glucose-induced cell apoptosis, the loss of MMP and the overproduction of ROS. In addition, under high glucose, MTS-hOGG1 transfection blocked the expression of Cytochrome C, but enhanced the expression of cytochrome c oxidase subunit 1 and NADPH-1. CONCLUSIONS: These findings indicated that high glucose induced cell apoptosis by causing the loss of MMP, the overproduction of ROS and mtDNA damage. Targeting DNA repair enzymes hOGG1 in mitochondria partly mitigated the high glucose-induced consequences, which shed new light for DR therapy.

Suppression of diabetic retinopathy with GLUT1 siRNA.

To investigate the effect of glucose transporter-1 (GLUT1) inhibition on diabetic retinopathy, we divided forty-eight mice into scrambled siRNA, diabetic scrambled siRNA, and GLUT1 siRNA (intravitreally injected) groups. Twenty-one weeks after diabetes induction, we calculated retinal glucose concentrations, used electroretinography (ERG) and histochemical methods to assess photoreceptor degeneration, and conducted immunoblotting, leukostasis and vascular leakage assays to estimate microangiopathy. The diabetic scrambled siRNA and GLUT1 siRNA exhibited higher glucose concentrations than scrambled siRNA, but GLUT1 siRNA group concentrations were only 50.05% of diabetic scrambled siRNA due to downregulated GLUT1 expression. The diabetic scrambled siRNA and GLUT1 siRNA had lower ERG amplitudes and ONL thicknesses than scrambled siRNA. However, compared with diabetic scrambled siRNA, GLUT1 siRNA group amplitudes and thicknesses were higher. Diabetic scrambled siRNA cones were more loosely arranged and had shorter outer segments than GLUT1 siRNA cones. ICAM-1 and TNF-α expression levels, adherent leukocyte numbers, fluorescence leakage areas and extravasated Evans blue in diabetic scrambled siRNA were higher than those in scrambled siRNA. However, these parameters in the GLUT1 siRNA were lower than diabetic scrambled siRNA. Together, these results demonstrate that GLUT1 siRNA restricted glucose transport by inhibiting GLUT1 expression, which decreased retinal glucose concentrations and ameliorated diabetic retinopathy.

Curcumin inhibits human retinal pigment epithelial cell proliferation.

Proliferative vitreoretinopathy (PVR) is a common cause of intraoperative failure following retinal reattachment surgery and is mediated in part through the migration, de-differentiation and proliferation of retinal pigment epithelial (RPE) cells. Given the cytotoxic effects of curcumin on epithelial and endothelial cells, in this study, we assessed the effects of curcumin on human RPE (hRPE) cell proliferation. WST-1 analysis revealed that curcumin significantly inhibited primary hRPE cell proliferation in a dose- and time-dependent manner (P<0.001) with the greatest inhibition observed at the dose of 15 µg/ml curcumin. Flow cytometric analysis indicated that the cytotoxic effects of curcumin on hRPE cell proliferation were mediated by cell cycle arrest at the G0/G1 phase and the induction of apoptosis (both P<0.001), which was confirmed by ultrastructural analysis using transmission electron microscopy. Furthermore, western blot analysis revealed that curcumin induced p53 and p21(WAF1/CIP1) expression with a concomitant decrease in proliferating cell nuclear antigen protein levels (P<0.05). Curcumin effectively inhibited primary hRPE cell proliferation, which may be mediated by the p53 pathway. Further in vivo studies are required in order to fully explore the therapeutic potential of curcumin for PVR.