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In recent years,with the widespread application of highly effective antiretroviral therapy(HAART), the incidence of human immunodeficiency virus(HIV)and acquired immunodeficiency syndrome(AIDS)related eye complications was significantly reduced. The absolute number of patients infected with HIV and AIDS increased year by year, and the survival rate increased and the survival time prolonged. The clinical manifestations of associated ocular complications in these patients are variable, affecting almost all ocular structures. At present, there is a lack of large-scale and long-term systematic observation of eye lesions in HIV-infected and AIDS patients in China. Misdiagnosis and missed diagnosis occur in many hospitals and even in some of the top-three hospitals. This not only delays the treatment of patients, but also easily cause iatrogenic transmission. Therefore, ophthalmologists and even other medical workers should enhance their knowledge of HIV/AIDS. This paper reviews the common complications of non-infection, opportunistic infection, and immune reconstitution inflammatory response syndrome(IRIS)in the HIV/AIDS patients, and discusses the manifestations and research progress of posterior ocular complications of HIV/AIDS.

The expression patterns and functional roles of miRNAs in retinoblastoma (RB) are poorly understood, especially those involved in chemoresistance. Here, we validated the expression pattern of 20 potential RB-suppressive miRNAs and confirmed that miR-184 is the most significantly decreased miRNA in human RB tissues, as well as chemoresistant cell line. Bioinformatic and molecular analyses revealed that SLC7A5 has three binding sites of miR-184 and significantly increased in RB tissues. miR-184 negatively correlated with SLC7A5 expression in RB tissues and mainly target position 2494-2513 of the SLC7A5 3′UTR to inhibit its expression. Furthermore, enforced expression of miR-184 reversed the oncogenic roles of SLC7A5 on proliferation, migration, and invasion of RB cells. In addition, miR-184 also enhances chemosensitivity of RB cells via inducing apoptosis and G2/M cell cycle arrest. Molecular studies revealed that miR-184-decreased phosphorylation status of known DNA damage repair sensors of the ATR/ATM pathways and induced persistent formation of γH2AX foci depend on targeting SLC7A5, leading to persistent DNA damage. Thus, targeting the miR-184/SLC7A5 pathway will provide new opportunities for drug development to reverse chemotherapeutic resistance in RB.

AIM:To compare the effectiveness of inverted internal limiting membrane flap(ILMF)coverage combined with sterile air tamponade or C3F8-filled surgery for idiopathic macular hole(IMH). METHODS: In this retrospective study, 165 patients(175 eyes)who underwent pars plana vitrectomy(PPV)combined with inverted ILMF coverage were evaluated. The surgeries were performed by one surgeon at the Renmin Hospital, Wuhan University between January 2014 and June 2017. The patients were divided into sterile air(Group A)and C3F8-filled(Group B)groups, based on the technique used for intraocular tamponade. With a minimum 3-month follow-up, pre- and post-operative best corrected visual acuity(BCVA), macular hole closure rate, and major postoperative complications were analyzed. RESULTS: Both groups showed significant improvement in visual acuity at 1 and 3mo postoperatively(PPPPPCONCLUSION: We postulate that PPV combined with inverted ILM flap is a safe and effective method for surgical management of IMH. Compared to C3F8-filling, sterile air tamponade can avoid IOP elevation; it may replace C3F8-filling in PPV for IMH.

AIM: To explore the effect of ciliary neurotrophic factor (CNTF) on retinal ganglion cell (RGC)-5 induced by hydrogen peroxide (H2O2). METHODS: After cell adherence, RGC-5 culture medium was changed to contain different concentrations of H2O2 from 50 to 150 µmol/L at four time points (0.5, 1, 1.5 and 2h) to select the concentration and time point for H2O2 induced model. Two different ways of interventions for injured RGC-5 cells respectively were CNTF as an addition in the culture medium or recombinant lentiviral plasmid carrying CNTF gene transfecting bone mesenchymal stem cells (BMSCs) for co-culture with RGC-5. RESULTS: Compared to the control group, H2O2 led to RGC-5 death closely associated with concentrations and action time of H2O2 and we chose 125 µmol/L and 2h to establish the H2O2-induced model. While CNTF inhibited the loss of RGC-5 cells obviously with a dose-dependent survival rate. Nevertheless two administration routes had different survival rate yet higher rate in recombinant lentiviral plasmid group but there were no statistically significant differences. CONCLUSION: Both the two administration routes of CNTF have effects on RGC-5 cells induced by H2O2. If their own advantages were combined, there may be a better administration route.

AIM: To observe the concentration of RBP4 and IL-6 in vitreous of proliferative diabetic retinopathy(PDR). METHODS: A total of 65 patients(66 eyes)were enrolled in Department of Ophthalmology, Renmin Hospital of Wuhan University from February 2017 to July 2017 with the informed consent. The patients were divided into PDR group(23 cases)and NPDR group(16 cases). Twenty-six patients without diabetic mellitus(DM)served as control group. The demography was matched among the groups, but the course of DM, the blood glucose level and the HbA1c level were elevated in the PDR group and the NPDR group(all PRESULTS: The concentration of RBP4 in PDR group, the NPDR group and control group were 13.68±2.66, 11.03±1.12, 10.45±1.17μg/mL, and the concentration of IL-6 were 56.0±10.27, 20.92±5.77, 10.26±1.91pg/mL. RBP4 and IL-6 concentrations were elevated in PDR group compared with NPDR group and control group, with significant difference among three groups(F=12.135, 161.167; PPP>0.05). Pearson correlation coefficient was significant positive between RBP4 concentration and IL-6 concentration(r=0.606, P=0.001). CONCLUSION: RBP4 is probability involved in the inflammation pathogenesis of PDR. These results indicate that RBP4 could be a new target for the diagnosis and treatment of PDR.

Familial exudative vitreoretinopathy(FEVR)is a hereditary disease associated with abnormal angiogenesis in the pediatric period. The most prominent finding of the disease is avascularity in the peripheral retina.Whereas, the phenotypic features are variable. In some minor cases, missed diagnosis would happened due to asymptom, while, in severe FEVR, neovascularization, retinal exudation, retinal folds, macular heterotopy and retinal detachment may occur and give rise to extremely poor vision or even blindness. Mutations in the FZD4, LRP5, NDP, TSPAN12, ZNF408, and KIF11 genes have been reported to contribute to FEVR with X-linked recessive, autosomal dominant, and autosomal recessive inheritance manners. We have summarized aspects of pathogenesis, clinical features and classification, mutations genes as well as diagnosis and treatment of FEVR in this review.

Given the poor prognosis of proliferative diabetic retinopathy(PDR), the morbidity of PDR has also increased recent years. Modern surgery has undergone a very impressive development over the last 10a due to the evolution of methods, techniques and extension of surgical indications. In this article, we will review the current choices of the surgery time, perioperative managements, as well as the methods of the vitrectomy.

AIM: To evaluate the long-term safety and efficacy of vitrectomy and internal limiting membrane (ILM) peeling with or without gas tamponade for highly myopic foveoschisis. METHODS: We performed an open-label, observer-blinded clinical trial of 85 patients with myopic foveoschisis between 2000 and 2012. Patients were randomly allocated to one of two groups, those who received vitrectomy and ILM peeling without gas tamponade (no-gas group) or those who with gas tamponade (gas group) and follow up at least 5y. RESULTS: Visual acuity of gas group improved from 0.82±0.33 to 0.79±0.73 in 6mo, improved to 0.71±0.67 in 1y and within this range in the following 4y. Visual acuity of no-gas group improved from 0.81±0.46 to 0.78±0.66 in 6mo, improved to 0.70±0.65 in 1y. The finial visual acuity of two groups were significantly increased compared with the baseline (P

AIM: To investigate the effect of HtrA1 on the proliferation, migration and apoptosis of human retinal pigment epithelium (RPE) cells in the light injured model, as well as the expression of the apoptosis related molecules. METHODS: The human RPE cell line ARPE-19 was exposed to blue light to establish the light injured model. The cells were transfected with HtrA1 siRNA to knockdown HtrA1 expression. Subsequent expression of HtrA1 was determined by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. Changes in cell proliferation, migration and apoptosis were assessed by cell counting kit-8 (CCK-8), Transwell assay and flow cytometry respectively, as well as changes in the mRNA and protein levels of Bax, Caspase-3 and Bcl-2 expression. RESULTS: HtrA1 was highly expressed in ARPE-19 cells after blue light irradiation. Knockdown of HtrA1 expression inhibited the proliferation, migration and apoptosis of the blue-light-irradiated ARPE-19 cells (P

AIM: To evaluate the effectiveness of pars plana vitrectomy(PPV)combined with inverted internal limiting membrane(ILM)flap technique for macular hole retinal detachment(MHRD)of high myopia. METHODS: This was a retrospective case series. Totally 27 patients(27 eyes)who were diagnosised with MHRD of high myopia and underwent vitrectomy combined with inverted ILM flap covering technique were eIlrolled in this study. The diopter was ≥-6.00D and axial length was ≥26mm. The mean age was 53.69±7.23 years. And there 9 males and 18 females. The logarithm of the minimum angle of resolution(LogMAR)best-corrected visual acuity(BCVA)was 1.41±0.28. All patients were performed PPV with inverted ILM flap, resected the vitreous gel and cortex completely. Bright blue G stained the ILM around the fovea. The ILM was peeled off around the MH, and some portion of the ILM flap was left attached to the edge of the MH. Covering the MH with the ILM flap.Then, C3F8 gas or silicone oil was injected into the vitreous cavity. The mean follow-up was more than 6mo and BCVA, MH closure, retinal reattachment, complications were retrospectively observed. RESULTS: After surgery, visual acuity improved in 21 eyes(78%), unchanged in 4 eyes(15%), decreased in 2 eyes(7%). The mean LogMAR BCVA was 0.84±0.40, the difference was significant(t=7.32, PCONCLUSION: PPV combined with inverted internal limiting membrane flap is an effective and safe management for the MHRD of high myopia.

Purpose: The present study aimed to investigate whether cervical vagal nerve stimulation (VNS) could prevent retinal ganglion cell (RGC) loss and retinal dysfunction after ischemia/reperfusion (I/R) injury.Methods: First, rats were randomly divided into sham group (n = 4) and VNS group (n = 12). Activation of the nodose ganglia (NOG), nucleus of the solitary tract (NTS), superior salivatory nucleus (SSN), and pterygopalatine ganglion (PPG) neural circuit were evaluated by c-fos expression at 0 h after sham VNS and at 0 h (n = 4), 6 h (n = 4), 72 h (n = 4) after VNS. Secondly, rats were randomly assigned to I/R group (pressure-induced retinal ischemia for 1 h and reperfusion for 1 h in the right eye, n = 16) and I/R+VNS group (right cervical VNS for 2 h during the I/R period, n = 16). The left eye of each rat served as a control. Electroretinogram (ERG), RGC numbers, tumor necrosis factor-α (TNF-α) and vasoactive intestinal polypeptide (VIP) levels in retina were determined. Additionally, the level of VIP in PPG was evaluated.Results: In the first part of the study, compared with the sham group, the VNS group exhibited significantly increased expression of c-fos in NOG, NTS, SSN, and PPG tissues at 0, 6, and 72 h. In the second part of the study, compared with left eyes, retinal function in right eyes (as assessed by the a-wave, b-wave and the oscillatory potential amplitudes of ERG and RGC data) was significantly decreased by I/R. The decreased retinal function was attenuated by VNS. In addition, I/R induced an increase in inflammation, which was reflected by elevated TNF-α expression in the retina. VNS significantly attenuated the increase in I/R-induced inflammation. Moreover, VIP expression in the retina and PPG, which may contribute to the inhibition of the inflammatory response, was significantly increased after VNS.Conclusion: VNS could protect against retinal I/R injury by downregulating TNF-α. Upregulation of VIP expression due to activation of the NOG-NTS-SSN-PPG neural circuit may underlie to the protective effects of VNS.

AIM: To observe the expression of proline hydroxylase domain 2 (PHD2) in the retina of diabetic rats and investigate the relationship between PHD2 and relevant intraocular vascular proliferation factors. METHODS: Sixty male specific pathogen free (SPF) Sprague-Dawley (SD) rats were randomly divided into two groups: the diabetic group and the control group. The rats in the diabetic group were intraperitoneally injected with 60 mg/kg (0.60 mL/100g) of streptozotocin to induce a diabetic rat model. The rats in the control group were injected with an equal volume of sodium citrate buffer solution by the same method. Hematoxylin-eosin (HE) staining and immumofluorescence (IF) method were adopted to observe the pathological changes of retinal tissues and the expression of PHD2, glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF) by 8wk. RT-PCR method was applied to detect the expressions of mRNA of PHD2, VEGF and GFAP. The relationship between PHD2 and other vascular proliferation factors was analyzed. RESULTS: HE staining showed that there was the retinal tissue edema in the diabetic group, and the arrangement was in disorder, and proliferation could be seen. IF staining: in the retina of normal rats, PHD2 was not expressed, GFAP and VEGF were mainly expressed in astrocytes; while in the diabetic rats, PHD2, GFAP and VEGF staining showed strong positivity in all retinal layers, mainly in neurogliocytes. PHD2 was co-expressed with VEGF and GFAP. The mRNA expression levels of PHD2, GFAP and VEGF in the diabetic group were obviously higher than that in the control group,respectively 1.83 times, 1.75 times and 2.08 times. The difference had statistical significance (P

Letter to the editor

AIM: To determine the optimal concentration for inducing the differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) into neuron-like cells, although it is understood that all-trans retinoic acid (ATRA) regulates cell proliferation in the nervous system by modulating the balance between mitosis and apoptosis. METHODS: The abilities of ATRA to promote apoptosis as well as neural differentiation were assessed in cultured hUC-MSCs by morphological observation, MTT assay, annexin V-FITC/PI flow cytometry and immunocytochemistry. RESULTS: The data showed that low concentrations of ATRA (0.5 µmol, 0.25 µmol) had no effect on the number of cells. However, treatment with 1.0 µmol or 2.0 µmol ATRA induced a 24.16% and 52.67% reduction in cell number, respectively, compared with vehicle-treated cultures. Further, 4.0 µmol ATRA had a potent effect on cell number, with almost no adherent cells recovered after 24h. We further showed that 0.5 µmol ATRA caused these cells to express characteristic markers of neuronal progenitor cells. CONCLUSION: Taken together, we conclude that ATRA has a dose-dependent influence on the neural differentiation and apoptosis of hUC-MSCs. These findings have implications on the use of ATRA-differentiated hUC-MSCs for the study of neural degeneration diseases.

Astaxanthin is a carotenoid widely found in marine organisms and microorganisms. With extensive use in nutraceuticals, cosmetics, and animal feed, astaxanthin will have the largest share in the global market for carotenoids in the near future. Owing to its unique molecular features, astaxanthin has excellent antioxidant activity and holds promise for use in biochemical studies. This review focuses on the observed health benefits of dietary astaxanthin, as well as its underlying bioactivity mechanisms. Recent studies have increased our understanding of the role of isomerization and esterification in the structure–function relationship of dietary astaxanthin. Gut microbiota may involve the fate of astaxanthin during digestion and absorption; thus, further knowledge is needed to establish accurate recommendations for dietary intake of both healthy and special populations. Associated with the regulation of redox balance and multiple biological mechanisms, astaxanthin is proposed to affect oxidative stress, inflammation, cell death, and lipid metabolism in humans, thus exerting benefits for skin condition, eye health, cardiovascular system, neurological function, exercise performance, and immune response. Additionally, preclinical trials predict its potential effects such as intestinal flora regulation and anti-diabetic activity. Therefore, astaxanthin is worthy of further investigation for boosting human health, and wide applications in the food industry. [ABSTRACT FROM AUTHOR]

AIM: To investigate the time-effect relationship between the expression of rhodopsin and recoverin and photoreceptor damage induced by N-nethl-N-nitrosourea(MNU). METHODS: Thirty-six 7-week old Sprague-Dawley(SD)rats were intraperitoneally injected with MNU(60mg/kg)and were put to death by dislocation of cervical vertebra 6, 12, 24h; 3, 7d after injection(6 per group), respectively. As a control, six rats were injected with phosphate buffer saline(PBS)5mL/kg and sacrificed on d3 after injection. The degree of photoreceptor apoptosis was detected by HE staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL)and transmission electron microscope(TEM)in the right eyes. The mRNA expressions of rhodopsin and recoverin were detected different time after injection by Western blot and immunohistochemical method in the left eyes. RESULTS: The dissolution of photoreceptor nucleus and apoptosis body were first perceived at 12h by TEM; most of cells at outer nuclear layer were presented positive reaction. The apoptotic index reached peak(29.7%±2.3%)at 24h which was coincided with the observation of TEM. The results of immunohistochemistry displayed that rhodopsin and recoverin were on a declining curve with time extension. Furthermore, the results of Western blot indicated that rhodopsin had dramatic decline at 6h after injection(P<0.05), and extremely significant difference comparing to control group after 12h(P<0.01); while recoverin dramatic declined at 12h, and extremely significant difference after 24h(P<0.01). CONCLUSION: 60mg/kg MNU intraperitoneally injection one-time may specifically induce photoreceptor apoptosis, The mechanism of down-regulation of rhodopsin and recoverin may be related to the selected apoptosis of photoreceptors.

AIM: To compare the best corrected visual acuity (BCVA) between Verteporfin with photodynamic therapy (PDT) and intravitreal anti-vascular endothelial growth factor (anti-VEGF) in patients with myopic choroidal neovascularization (CNV).METHOD: Published literature from Medline, Premedline, Embase and the Cochrane Library from inception until November 2013 were retrieved. All studies evaluating the BCVA between Verteporfin with PDT and intravitreal anti-VEGF for myopic CNV were included. The results were pooled using mean difference (MD), a corresponding 95% confidence interval (CI).RESULTS:Finally, five studies enrolled 349 eyes were included in the meta-analysis. We inferred that the BCVA of myopic CNV after the treatment of anti-VEGF was significantly better compared with Verteporfin with PDT (MD=0.25, 95％CI:0.17-0.33, Z=5.97, PCONCLUSION: This meta-analysis suggests that intravitreal anti-VEGF could have a better BCVA after treatment than Verteporfin with PDT for myopic CNV.

AIM:To investigate the protective mechanism of Gingko Biloba extract (EGb761) on the ability of retinal pigment epithelial (RPE) cells to resist light-induced damage in a comparative proteomics study.METHODS:Human RPE cells (ARPE-19) were randomly distributed to one of three groups:normal control (NC group) and light-damaged model without or with EGb761 group (M and ME groups, respectively). The light-damaged model was formed by exposing to white light (2 200±300)lx for 6h. The RPE cells in ME group were conducted with EGb 761 (100μg/mL) before light exposure. The soluble cellular proteins extracting from each groups were separated by two-dimensional electrophoresis and stained by silver staining. Different proteins in the profiles of the gels were analyzed by Image Master Software. Two-fold expressing protein spots were identified by Matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) mass spectrometry.RESULTS: NC, M and ME groups displayed 1 892±71, 2 145±23 and 2 216±85 protein spots, respectively. We identified 33 proteins with different expression levels between the NC and M groups, 25 proteins between the M and ME groups, and 11 proteins between the NC and ME groups. MALDI-TOF/TOF mass spectrometry successfully identified 16 proteins, including metabolic enzymes, cytoskeletal proteins, anti-oxidation proteins, and others.CONCLUSION:Differences in some important proteins, such as cathepsin B, heat shock protein, and cytochrome creductase, indicated that multiple pathways may be induced in light-damaged RPE cells and the protective effect of EGb761.

AIM: To evaluate the clinical efficacy of intravitreous injection of Lucentis combined with argon laser photocoagulation on retinal macroaneurysm.METHODS: A retrospective observation about intravitreous injection of Lucentis combined with argon laser photocoagulation was performed on 9 patients(9 eyes)with retinal macroaneurysms with macular edema between January 2011 and July 2013. Through the collection of clinical data in patients best-corrected visual acuity, change of the retinal macroaneurysm, optical coherence tomography and fluoresce in fundus angiography before therapy and 1 mouth,3 mouths after therapy, comparative analysis the changes in best-corrected visual acuity and central macular retinal thickness(CMT)between before and after treatment.RESULTS: Followed for more than 3 months, all patients' best-corrected visual acuity were improved obviously, the difference was significant(PPCONCLUSION:Intravitreous injection of Lucentis combined with argon laser photocoagulation is effective and security to improving visual acuity of retinal macroaneurysms with macular edema.