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Abstract Mutations in the extracellular matrix gene Fibrillin-2 (FBN2) are related to genetic macular degenerative disorders including age-related macular degeneration (AMD) and early-onset macular degeneration (EOMD). It was reported that the retinal protein expression of FBN2 was reduced in patients with AMD and EOMD. The effect of exogenously supplied fbn2 recombinant protein on fbn2-deficiency-related retinopathy was not known. Here we investigated the efficacy and molecular mechanism of intravitreally applied fibrin-2 recombinant protein in mice with fbn2-deficient retinopathy. The experimental study included groups (all n = 9) of adult C57BL/6J male mice which underwent no intervention, intravitreal injection of adeno-associated virus (AAV) empty vector or intravitreal injection of AAV-sh-fbn2 (adeno-associated virus for expressing short hairpin RNA for fibrillin-2) followed by three intravitreal injections of fbn2 recombinant protein, given in intervals of 8 days in doses of 0.30 μg, 0.75 μg, 1.50 μg, and 3.00 μg, respectively. Eyes with intravitreally applied AAV-sh-fbn2 as compared to eyes with injection of AAV-empty vector or developed an exudative retinopathy with involvement of the deep retinal layers, reduction in axial length and reduction in ERG amplitudes. After additional and repeated application of fbn2 recombinant protein, the retinopathy improved with an increase in retinal thickness and ERG amplitude, the mRNA and protein expression of transforming growth factor-beta (TGF-β1) and TGF-β binding protein (LTBP-1) increased, and axial length elongated, with the difference most marked for the dose of 0.75 μg of fbn2 recombinant protein. The observations suggest that intravitreally applied fbn2 recombinant protein reversed the retinopathy caused by an fbn2 knockdown.

To examine the mechanism of ocular axial elongation in myopia, guinea pigs (age: 2–3 weeks) which either underwent unilateral or bilateral lens-induced myopization (group 1) or which were primarily myopic at baseline (group 2) received unilateral intraocular injections of amphiregulin antibody (doses: 5, 10, or 15 μg) three times in intervals of 9 days. A third group of emmetropic guinea pigs got intraocular unilateral injections of amphiregulin (doses: 0.25, 0.50 or 1.00 ng, respectively). In each group, the contralateral eyes received intraocular injections of Ringer's solution. In intra-animal inter-eye comparison and intra-eye follow-up comparison in groups 1 and 2, the study eyes as compared to the contralateral eyes showed a dose-dependent reduction in axial elongation. In group 3, study eyes and control eyes did not differ significantly in axial elongation. Immunohistochemistry revealed amphiregulin labelling at the retinal pigment epithelium in eyes with lens-induced myopization and Ringer's solution injection, but not in eyes with amphiregulin antibody injection. Intraocular injections of amphiregulin-antibody led to a reduction of lens-induced axial myopic elongation and of the physiological eye enlargement in young guinea pigs. In contrast, intraocularly injected amphiregulin in a dose of ≤1 ng did not show a significant effect. Amphiregulin may be one of several essential molecular factors for axial elongation.

Ocular toxocariasis(OT)is an ocular parasitic disease involving ocular tissue infection by the ascarid-omatidae nematode. OT is usually caused by toxocara canis or toxocara cati. Susceptible population are more likely to be affected by their own hygiene, the frequency of exposure to dogs and cats, and the consumption of food or water contaminated with toxocariasis larvae. Most cases have been reported worldwide in children, but cases in adults have also been reported in recent years, which may be due to the lack of systematic induction and summary of its diagnosis, treatment and prognosis. In this paper, the four clinical manifestations of OT, advanced noninvasive diagnostic techniques, and laboratory immunological tests were sorted out and supplemented by reviewing domestic and international literature. Meanwhile, this paper introduced the treatment progress of OT in recent years, such as the combination of anthelmintic and hormone, and the application of intravitreal injection and vitreous surgery. It is expected that clinicians should pay more attention to this disease, improve the accuracy of early diagnosis of toxocariasis and protect patients' vision.

AIM: To evaluate the one-year outcome of intravitreal conbercept injections for the treatment of choroidal neovascularization secondary to pathological myopia(pm-CNV)by optical coherence tomography angiography(OCTA).METHODS: The medical records of 26 consecutive eyes of 23 patients who received intravitreal injections of conbercept for pm-CNV with a follow-up of 1y were retrospectively reviewed. All the patients were diagnosed by fundus fluorescein angiography(FFA)and OCTA at the first visit. All approaches were performed as “1+PRN” treatment. Outcomes included best-corrected visual acuity(BCVA), central foveal thickness(CFT)and the mean CNV area by OCTA.RESULTS: Mean BCVA improved from(0.66±0.51)at baseline to(0.39±0.38)at 1y(t=3.528, P=0.004). The CFT before treatment and after 1y after were(275.08±48.74)μm and(205.15±43.74)μm respectively(t=4.630, P=0.001). The mean pm-CNV areas before treatment and after 1y treatment were(0.48±0.24)mm2 and(0.15±0.11)mm2 respectively, with a significant difference among them(t=5.329, P=0.000). Twenty-one eyes had no needs after the first treatment. Four eyes received 2 injections and only one eye received 3 injections. No severe adverse events were noted relevant to the therapy.CONCLUSION: Intravitreal conbercept can improve the vision and relieve CFT and CNV area for the treatment of pm-CNV with “1+PRN” by OCTA for 1y, however, long-term follow-up still need to be performed.

AIM: To investigate the cytotoxic effect of specific T cells from mice with experimental autoimmune uveitis (EAU) as well as their secreted interferon (IFN)-γ and interleukin (IL)-17A on murine photoreceptor (661W) cells. METHODS: An EAU model was established in female mice by injection of interphotoreceptor retinoid binding protein (IRBP) emulsion supplemented with complete Freund’s adjuvant (CFA) and Mycobacterium tuberculosis (TB). On day 12 after induction of EAU, specific T cells from spleen and lymph node tissues were isolated and cultured for 4d and the levels of IFN-γ and IL-17A in the supernatants were determined by enzyme-linked immunosorbent assays (ELISAs). T cells and their supernatants were added to 661W cells to observe the alteration of cell morphology; IFN-γ and IL-17A were separately added to 661W cells to observe the effect of IFN-γ and IL-17A on cell proliferation. RESULTS: The levels of IFN-γ and IL-17A in the T cell supernatants were 1568.64±38.79 pg/mL and 1456.57±46.98 pg/mL, respectively. The supernatants apparently inhibited 661W cell proliferation (P

Myopia is one of the most common eye diseases in the world. MicroRNAs(miRNAs)are small, non-protein-coded single-stranded RNAs with a length of about 20-25 nucleotides,which are widely involved in the process of post-transcriptional regulation of many physiological and pathological processes of organisms. It has attracted extensive attention for the regulation role of miRNAs in the process of induction and development of myopia in recent years. This article reviews the regulatory role and related signal pathways of miRNAs in the development of myopia. It will provide highlights for the understanding of molecular mechanism of myopia and benefit for potential molecular diagnosis of myopia in the future.

At present, myopia has become a public health disease worldwide, and its occurrence is mostly caused by genetic and environmental factors. Single nucleotide polymorphisms(SNPs)are the changes in single base at the genomic level caused by DNA sequence polymorphisms. In recent years, it is reported that the change of SNPs in myopic related gene loci is closely related to the occurrence and development of myopia. The present paper reviewed the current status of the association between SNPs of myopia-related genes and the development of myopia, providing a new insight into the future research of pathogenesis of myopia.

AIM: To systematically review the current evidence based on the efficacy and cost of Ex-PRESS implantation and trabeculectomy (Trab) for uncontrolled glaucoma. METHODS: Clinical trials were identified by electronic databases (PubMed, EMBASE, ISI Web of science and Cochrane library), and data, such as intraocular pressure (IOP), the complete and qualified success rate, the postoperative complications and the cost, were exacted from these relevant studies. Weighted mean difference (WMD), odds ratio (OR) and 95% confidence intervals (CIs) were calculated and were pooled using a random-effects model. RESULTS: Eleven relevant publications and two abstracts met the inclusion criteria. The efficacy of Ex-PRESS was similar to that of Trab in the percentage of IOP reduction (IOPR %) at 1, 2y (WMD: -2.01; 95% CI: -7.92-3.90; P=0.50 and WMD: 2.89; 95% CI: -8.05-13.83; P=0.60, respectively). Ex-PRESS possessed a significant higher complete and qualified success rate (OR: 1.59; 95% CI: 1.07-2.35; P=0.02 and OR: 1.74; 95% CI: 1.06-2.86; P=0.03, respectively). Moreover, Ex-PRESS exerted a significantly lower frequency of hypotony and hyphema than Trab (OR: 0.39; 95% CI: 0.21-0.72; P=0.003 and OR: 0.27; 95% CI: 0.10-0.69; P=0.003, respectively). However, there was no consistent result on the cost between the two groups according to the previous three studies. CONCLUSION: Both Trab and Ex-PRESS have equivalent efficacy in lowering IOP, yet Ex-PRESS had a lower risk of hypotony and hyphema than Trab. Nevertheless, whether the cost of Ex-PRESS was less than that of Trab should be further investigated to ensure evidence-based conclusion in the long run.

In view of the anatomical and physiological barrier of the ocular surface and the intraocular structure, the conventional ophthalmic agents cannot efficiently reach the lesion site. Currently, the different types of nanomaterials possess great advantages in delivering drugs due to their characteristics of small size, easy preparation, degradability, strong targeting and less irritation to biological tissue. As drug delivery carriers, nanomaterials have been widely used in ocular drug delivery so as to treat different types of eye diseases. In this paper, the applications of nanomaterials as drug delivery carriers in treating eye diseases are briefly reviewed.

AIM: To compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODS: A systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis.RESULTS: Three RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P≤0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All PPCONCLUSION: IVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.

AIM:To compare the efficacy and safety of combination of ranibizumab with photodynamic therapy (PDT) vs ranibizumab monotherapy in the treatment of age-related macular degeneration (AMD).METHODS:The Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Pubmed, and Embase were searched. There were no language or data restrictions in the search for trials. Only randomized controlled trials (RCTs) were included. Methodological quality of the literatures was evaluated according to the Jadad Score. RevMan 5.2.6 software was used to do the meta-analysis.RESULTS:Seven studies were included in our systematic review, among which four of them were included in quantitative analysis. The result shows that the ranibizumab monotherapy group had a better mean best corrected visual acuity (BCVA) change vs baseline at month 12 compared with that of the combination treatment group, and the statistical difference was significant (WMD, -2.61; 95% CI, -5.08 to -0.13; P=0.04). However, after the removal of one study, the difference between the two groups showed no significant difference (WMD, -2.29; 95% CI, -4.81 to 0.23; P=0.07). Meanwhile, no significant central retinal thickness (CRT) reduction was found in the combination treatment group and the ranibizumab monotherapy group at 12 months follow-up. Nevertheless, the combination group tended to have a greater reduction in CRT (WMD, -4.13μm; 95%CI, -25.88 to 17.63, P=0.71). The proportion of patients gaining more than 3 lines at month 12 in the ranibizumab group was higher than in the combination group and there was a significant difference (RR, 0.72; 95% CI, 0.54 to 0.95; P=0.02). Whereas there was no significant difference for the proportion of patients gaining more than 0 line at month 12 between the two groups (RR, 0.93; 95% CI, 0.76 to 1.15; P=0.52). The general tendency shows a reduction in ranibizumab retreatment number in the combination treatment group compared with the ranibizumab monotherapy group. As major adverse events, the differences in the number of eye pain, endophthalmitis, hypertension and arterial thromboembolic events were not significant between the two groups, and the incidence of serious adverse events in the two groups was very low.CONCLUSION:For the maintenance of vision, the comparison of the combination of ranibizumab with PDT vs ranibizumab monotherapy shows no apparent difference. Compared with the combination of ranibizumab and PDT, patients treated with ranibizumab monothearpy may gain more visual acuity (VA) improvement. The combination treatment group had a tendency to reduce the number of ranibizumab retreatment. Both the two treatment strategies were well tolerated.

AIM:To establish the model of age-related macular degeneration through blue light burning human retinal pigment epithelium(hRPE)cells in vitro and to investigate the possible mechanism of lycium barbarum polysaccharide(LBP)protecting the hRPE cells from blue light irradiation-induced damage.METHODS: hRPE cells were cultured in Dulbecco's modified eagle's medium with high glucose and were pretreated with different concentrations(0.01mg/mL, 0.1mg/mL and 1mg/mL, respectively)of LBP solution, respectively. Further, hRPE cells were irradiated with different intensities(2000±500 LUX)of blue light(wave length 470-520nm)for 12h and the cellular morphology was observed by inverted phase contrast microscopy for every sample. Using flow cytometry, the alterations in the levels of reactive oxygen species, mitochondrial membrane potential and apoptosis were determined, respectively. RESULTS: The level of reactive oxygen species in hRPE cells in blue-light treatment group was the highest, whereas the level in control group was the lowest. The fluorescent level of reactive oxygen species among different concentrations of LBP-treatment groups had specifically significant differences compared with that in blue light irradiation group(PPP>0.05). CONCLUSION: LBP can efficiently inhibit apoptosis induced by blue light irradiation in hRPE cells and 1mg/mL of LBP has the strongest protective ability in blue light irradiation-induced damage in hRPE cells. The possible mechanism may attribute to the protective effect of LBP in inhibiting the overgeneration of reactive oxygen species and apoptosis in hRPE cells.

To assess stereoacuity in a population-based sample of children and to examine ocular and systemic parameters related to stereoacuity.Using a random cluster sampling method, four- to 18-year-old children from kindergartens, elementary schools, junior high schools and senior high schools from a rural area and an urban area in the East Chinese province of Shandong were included in the school-based cross-sectional study. All participants underwent a comprehensive eye examination including assessment of cycloplegic refraction and measurement of stereoacuity using the Titmus Stereo test.Out of 6364 eligible children, 5780 (90.8%) children with a mean age of 10.1 ± 3.2 years (range: 4 to 18 years) participated. Mean (± standard deviation) stereoacuity was 50.2 ± 50.6 arc seconds. Stereoacuity improved significantly (P

Cognitive impairment is the most common neurologic sequelae after carbon monoxide (CO) poisoning, and the previous investigations have demonstrated that N-Butylphthalide (NBP) could exert a broad spectrum of neuroprotective properties. The current study aimed to investigate the effect of NBP on cognitive dysfunction in rats after acute severe CO poisoning. Rats were randomly divided into a normal control group, a CO poisoning group and a COCNBP group. The animal model of CO poisoning was established by exposure to CO in a chamber, and then all rats received hyperbaric oxygen therapy once daily, while rats in COCNBP group were administered orally NBP (6 mg/ 100g) by gavage twice a day additionally. The results indicated that CO poisoning could induce cognitive impairment. The ultrastructure of hippocampus was seriously damaged under transmission electron microscopy, and the expressions of calpain 1 and CaMK II proteins were significantly elevated after CO exposure according to the analysis of immunofluorescence staining and western blot. NBP treatment could evidently improve cognitive function, and maintain ultrastructure integrity of hippocampus. The expression levels of both calpain 1 and CaMK II proteins in COCNBP group were considerably lower than that of CO poisoning group (P < 0.05). Taken together, this study highlights the molecular mechanism of cognitive dysfunction in rats after CO exposure via the upregulation of both calpain 1 and CaMK II proteins. The administration of NBP could balance the expressions of calpain 1 and CaMK II proteins and improve cognitive function through maintaining ultrastructural integrity of hippocampus, and thus may play a neuroprotective role in brain tissue in rats with CO poisoning. [ABSTRACT FROM AUTHOR]

The addition reactions of the 16ehalf-sandwich complexes (p-cymene)M(S2C2B10H10) (1S, M = Ru; 2S, M = Os) and Cp*Ir(E2C2B10H10) (3S, E = S; 3Se, E = Se) with ethynylferrocene lead selectively to the 18ecomplexes (p-cymene)Ru(S2C2B10H9)(H2CCFc) (Fc = ferrocenyl) (4S), (p-cymene)Os(S2C2B10H9)(H2CCFc) (5S), Cp*Ir(S2C2B10H9)(H2CCFc) (6S) and Cp*Ir(Se2C2B10H9)(H2CCFc) (6Se), in which the alkyne is regio- and stereoselectively inserted into one of the M–E bonds that may further lead to metal-induced B–H activation, hydrogen atom transfer from the carborane viathe metal center to the inserted alkyne, and the generation of a M–B bond. In all complexes the S-η2-(Fc)C–C and C–B(M) moieties occupy a cisoidposition. The four new complexes are characterized by IR, MS, NMR spectroscopy and microanalysis, and the X-ray structural analysis of 4Sis performed. 4Swas observed to promote the uptake of anticancer drug daunorubicin in drug-resistant leukemia K562 cells. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of electroacupuncture (EA) on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lens-induced myopia (LIM). METHODS: Guinea pigs were randomly divided into normal control (NC) group, LIM group, LIM+SHAM acupoint (LIM+SHAM) group, and LIM+EA group. Animals in the NC group received no intervention, while those in other three groups were covered with -6.0 diopter (D) lenses on right eyes. Meanwhile, animals in the LIM+EA group received EA at Hegu (LI4) combined with Taiyang (EX-HN5) acupoints, while those in the LIM+SHAM group were treated at sham points. After treatments for 1, 2, and 4wk, morphological changes in ciliary muscles were observed with hematoxylin and eosin (H&E) staining and nick end labeling (TUNEL), and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Additionally, the adenosine triphosphate (ATP) contents were also determined in ciliary muscles. RESULTS: Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group. The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups, whereas those in the LIM+EA group improved significantly. TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups, whereas reduced in the LIM+EA group. ATP contents showed a significant decrease in the LIM and LIM+SHAM groups, whereas increased after EA treatment. Compared with the NC group, the dynamin-related protein 1 (DRP1), Caspase3, and apoptotic protease activator 1 (APAF1) levels were significantly increased in the LIM group and decreased in the LIM+EA group. CONCLUSION: The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

The occurrence and development of many eye diseases are closely related to genetic and environmental factors, among which epigenetic modification is an important bridge connecting genetic and environmental factors. It can affect the levels of related genes by influencing gene transcription or translation, thereby playing a role in the pathogenesis of ocular diseases. DNA methylation is an important part of epigenetic modification which is usually regulated by three processes: de novo methylation, maintenance methylation, and demethylation, and plays an essential role in regulating gene expression. At present, researchers have conducted that DNA methylation plays an important role in repair of damage to corneal endothelium, mitochondrial dynamics regulation and diabetic retinopathy, oxidative stress response and cataracts and other eye diseases, providing new ideas in the treatment of related ocular diseases. This study presented a brief review of the role of DNA methylation in the development of related ocular diseases and provided new perspectives and directions for the screening, diagnosis, and treatment of eye diseases.

AIM: To investigate the regulatory effect of miR-223-3p on the expression of transcription factor Rbpj and on the differentiation of Th1 and Th17 cells in experimental autoimmune uveitis(EAU)rats.METHODS: The regulatory role of miR-223-3p in Rbpj gene expression was investigated by a dual luciferase expression reporter system. In the present study, 24 female Lewis rats were randomly divided into EAU model group, normal control(NC)group and blank control(BC)group, and each group included 8 rats. The EAU model group was injected with interphotoreceptor retinoid-binding protein(IRBP)emulsion containing Mycobacterium tuberculin H37RA and complete Freund's adjuvant to induce uveitis, while the NC group was injected with an equal volume of emulsion without IRBP peptide. The rats in the BC group received the same volume of sterile saline solution. At 12d after immunization, the spleen, lymph node and eye tissues in both groups were aseptically isolated, and the expression levels of miR-223-3p and Rbpj RNAs were detected by real-time quantitative PCR(Q-PCR); Meanwhile, the expression levels of Rbpj, IFN-γ and IL-17 proteins were detected by ELISA, and the levels of Th1 and Th17 cell lineages in each tissue from each groups were detected by flow cytometry. RESULTS: The results of dual fluorescein assay indicated that Rbpj was the target gene which regulated by miR-223-3p. At 12d after immunization, compared with NC group, the relative expression levels of miR-223-3p in spleen, lymph node and eye tissues from EAU model rats were 0.33±0.29, 0.11±0.12 and 0.18±0.11, respectively, accompanied by the down-regulated expression, and the differences were statistically significant(all P0.05); ELISA results revealed that the expression levels of RBPJ, IFN-γ and IL-17 proteins in all tissues from EAU rats at 12d after immunization were significantly higher than those in the NC group( all P0.05); Meanwhile, flow cytometry results showed that the proportions of Th1 and Th17 cell lineages in all tissues from EAU model group were significantly higher than those from the NC group at 12d after immunization, and the differences were statistically significant(all P0.05). CONCLUSION: The miR-223-3p can negatively regulate the expression of the transcription factor Rbpj of Notch signaling pathway. The down-regulated miR-223-3p expression in EAU rats can increase the expression levels of Rbpj gene and protein, and aggravate the differentiation of Th1 and Th17 cells and the expression levels of related molecules IFN-γ and IL-17, which in turn affect the development of uveitis.