Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck.

Avian eggshell color is an interesting genetic trait. Here, we report that the blue eggshell color of the domestic duck is caused by two cis-regulatory G to A transitions upstream of ABCG2, which encodes an efflux transporter. The juxtaposed blue eggshell allele A-A exhibited higher promoter activity and stronger nuclear protein binding capacity than the white eggshell allele G-G. Transcription factor analysis suggested differential binding capability of CTCF between blue eggshell and white eggshell alleles. Knockdown of CTCF expression significantly decreased the promoter activity of the blue eggshell but not the white eggshell allele. DNA methylation analysis revealed similar high methylation of the region upstream of the CTCF binding sites in both blue-eggshelled and white-eggshelled ducks. However, DNA methylation levels downstream of the binding sites were decreased and 35% lower in blue-eggshelled ducks than in white-eggshelled ducks. Consistent with the in vitro regulatory pattern of causative sites, ABCG2 exhibited higher expression in uteruses of blue-eggshelled ducks and also showed polarized distribution in their endometrial epithelial cells, distributing at the apical surface of endometrial epithelial cells and with orientation toward the uterine cavity, where the eggshell is pigmented. In conclusion, our results suggest that two cis-regulatory SNPs upstream of ABCG2 are the causative mutations for blue eggshells in ducks. The blue eggshell variant up-regulated ABCG2 expression through recruiting CTCF binding, which may function as a barrier element to shield the downstream region from high methylation levels present upstream. ABCG2 was identified as the only candidate causative gene for blue eggshells; it may function as an efflux transporter of biliverdin to the uterine cavity.

Reducing the carbon emission from agricultural production in China: do land transfer and urbanization matter?

Urbanization and land transfer have triggered a profound reform of the Chinese agricultural sector since reform and opening, leading to a continuous rise in agricultural carbon emissions. However, the impact of urbanization and land transfer on agricultural carbon emissions is not widely understood. Therefore, based on the panel data covering 30 provinces (cities) in China from 2005 to 2019, we adopted a panel autoregressive distributed lag model and a vector autoregressive model to empirically explore the causal relationship between land transfer, urbanization, and agricultural carbon emissions. The main conclusions are as follows: (1) Land transfer can significantly reduce carbon emissions from agricultural production in the long run, while urbanization has a positive effect on agricultural carbon emissions. (2) In the short run, land transfer has a significant positive impact on agricultural carbon emissions, and urbanization also has a positive impact on the carbon emissions of agricultural production, but in insignificant ways. (3) There is two-way causality between land transfer and agricultural carbon emission, and between urbanization and land transfer is the same, but urbanization is the one-way Granger cause of agricultural carbon emissions. Finally, some suggestions are provided for low-carbon agriculture development: the government should encourage the transfer of land management rights and guide high-quality resources to gather in green agriculture.

Anti-Vascular Endothelial Growth Factor Therapy Abolishes Glioma-Associated Endothelial Cell-Induced Tumor Invasion.

Tumor-remodeled endothelial cells not only facilitate the formation of tumor angiogenesis but also promote tumorigenesis. In this study, we aimed to explore the interaction between glioma-associated endothelial cells (GAEs) and glioma cells. We found that different subtypes of glioma owned distinct GAE abundance. Glioma patients with high GAE abundance exhibited poor prognosis. Both the results of the bioinformatics analysis and the in vitro co-culture system assay revealed that GAE promoted glioma cell invasion. Besides, anti-vascular endothelial growth factor (VEGF) therapy partially abolished the effects of GAE on gliomas. Moreover, anti-VEGF therapy upregulated IL-2 expression in GAE, and exogenous IL-2 administration inhibits GAE-induced glioma cell invasion. Collectively, our present study provides a novel outstanding of the interaction between GAE and glioma cells.

Long Non-coding RNA GAS5 Knockdown Attenuates H2O2-Induced Human Trabecular Meshwork Cell Apoptosis and Promotes Extracellular Matrix Deposition by Suppressing miR-29b-3p and Upregulating STAT3.

The long non-coding RNA GAS5 (GAS5) is reportedly implicated in glaucoma. However, its significance in human trabecular meshwork cells (HTMCs) remains largely unclear. Here, we investigated the effect of GAS5 on the function of HTMCs and its interaction with miR-29b-3p in HTMCs. We established an H2O2-induced oxidative injury model using HTMCs. RT-qPCR or western blotting was performed to examine the expression of the indicated genes. Luciferase reporter assay was used to determine the interaction between GAS5, miR-29b-3p, miR-29b-3p, and STAT3. CCK8 assay was used to assess the proliferative rate of HTMCs. Exposure to H2O2 increased the expression of Bax, cleaved caspase-3, and extracellular matrix (ECM) proteins, accompanied by reduced Bcl-2 expression. These H2O2-induced changes were effectively alleviated by GAS5 knockdown with sh-GAS5. MiR-29b-3p was directly regulated by GAS5. The effect of sh-GAS5 on ECM protein expression was also observed with the miR-29b-3p mimic. STAT3 was directly regulated by miR-29b-3p. MiR-29b-3p silencing alleviated STAT3 inhibition, followed by the restoration of cell vitality, Bax, Bcl-2, and cleaved caspase-3 expression, and ECM deposition. Our study is the first experimental investigation to shed light on a novel molecular mechanism of the GAS5/miR-29b-3p/STAT3 axis in an H2O2-induced oxidative injury model using HTMCs, which may offer a promising therapeutic approach against glaucoma.

Efficacy of microcatheter-assisted trabeculotomy on secondary glaucoma after congenital cataract surgery.

AIM: To evaluate efficacy of microcatheter-assisted trabeculotomy (MAT) in eyes with secondary glaucoma after congenital cataract surgery and explore its correlation with the different degree of trabeculotomy. METHODS: A retrospective analysis was conducted on patients who underwent the said procedure between September 2019 and September 2020. The patients were classified into two groups according to the degree of trabeculotomy (group 1: ≤240-degree; group 2: 240-360-degree). The intraocular pressure (IOP) and anti-glaucoma drugs before and after operation was collected during the 12-month follow-up. RESULTS: Totally 27 eyes of 25 patients were included: 11 (40.7%) eyes in group 1 and 16 (59.3%) eyes in group 2. The mean IOP of all patients was 34.67±9.18 mm Hg preoperatively and 8.74±4.32, 9.95±5.65, 14.39±5.30, 16.02±4.37, 15.82±3.28, and 16.19±3.56 mm Hg 1d, 1wk, 1, 3, 6, and 12mo after surgery, respectively. In all patients, there were significant differences in IOP at each time point (F=65.614, P<0.01). In each group, IOP after surgery was lower than that before surgery (all P<0.01), but there was no difference in the rate of IOP reduction between the two groups (P=0.246). Furthermore, the amount of anti-glaucoma medications reduced to 0.30±0.67 (0-2) at 12mo from 2.63±0.49 (2-3) preoperatively (P<0.01), and there was no difference between the two groups (P>0.05). At the end of follow-up, the partial success rate was 81.8% in group 1 vs 93.75% in group 2 (P=0.549). Various amount of intraoperative and postoperative hyphema occurred in all eyes, which spontaneously absorbed or cleaned through paracentesis and irrigation. No other serious complications was observed. CONCLUSION: MAT can effectively reduce IOP in patients with secondary glaucoma after congenital cataract surgery with a high success rate and safety. And it can be used as the first choice for the treatment of secondary glaucoma after surgery for congenital cataracts.

Dynamic Linkages among Climate Change, Mechanization and Agricultural Carbon Emissions in Rural China.

Climate change has become a major environmental issue facing all countries, having a significant effect on all aspects of agricultural production, such as the agricultural mechanization process and fertilizer use. Greenhouse gases produced by agricultural machinery and fertilizers during agricultural production are an important cause of climate change. On the basis of the above facts, researching the connection between agricultural mechanization, climate change, and agricultural carbon emissions is crucial for the development of low-carbon agriculture and for addressing climate change. We used a variety of econometric models and methods to analyze data from China's multiple provinces (cities) covering the years 2000 through 2019, in order to meet the research objectives. Furthermore, we utilized rainfall and sunlight as variables to assess climate change and adopted Granger tests to establish the link between rainfall, sunlight, agricultural mechanization, and carbon emissions in farming. The findings indicate a bidirectional causality relationship between rainfall, sunlight, agricultural mechanization, and carbon emissions in farming. Rainfall and sunlight are Granger causes of agricultural mechanization. Furthermore, agricultural mechanization has favorable effects on carbon emissions of agriculture, and climate change has long-term implications on agricultural mechanization and carbon emissions of agriculture. Finally, this paper investigated the green path suitable for the low-carbon development of Chinese agriculture, arguing that the government should formulate low-carbon agricultural policies by region and actively promote the upgrading of agricultural machinery.

The GABAB receptor mediates neuroprotection by coupling to G13.

G protein­coupled receptors (GPCRs) activate various mitogen-activated protein kinase (MAPK) pathways to regulate critical cell functions. ß-Arrestins mediate this mechanism for most GPCRs but not the GABAB receptor (GABABR). When coupled to the G protein Gi/o, GABABR phosphorylates the kinases ERK1 and ERK2. Here, we uncovered a distinct ß-arrestin­independent mechanism of MAPK pathway activation by GABABR. We found that GABABR also phosphorylated the kinase JNK downstream of activation of the small guanosine triphosphatases (GTPases) RhoA and Rac1 in primary mouse neurons. However, instead of Gi/o proteins, activation of this RhoA/Rac1-JNK pathway was mediated by G13. This pathway promoted the phosphorylation and accumulation of the postsynaptic scaffolding protein PSD95 and GABABR-mediated neuroprotection in granule neurons. In addition, this pathway synergized with a previously reported GABABR-mediated neuroprotection mediated by a Gi/o-dependent mechanism. GABABR agonists activated G13 with slower kinetics and lower potency than with which they activated Gi/o. Our findings reveal distinct, ß-arrestin­independent, context-specific synergistic mechanisms of MAPK activation by G protein­mediated GPCR signaling.

Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop.

BACKGROUND: The aim of this study was to compare the distribution characteristics and ocular pharmacokinetics of norvancomycin (NVCM) in ocular tissues of the anterior segment between continuous topical ocular instillation and hourly administration of eye drop in rabbits. METHODS: Sixty rabbits were randomly divided into two groups: continuous topical ocular instillation drug delivery (CTOIDD) group and eye drop (control) group. In the CTOIDD group, NVCM solution (50 mg/mL) was perfused to the ocular surface using the CTOIDD system at 2 mL/h up to 10 h and the same solution was administered at one drop (50 µL) per hour for 10 h in the control group. Animals (N=6 per time-point per group) were humanely killed at 2, 4, 6, 10, and 24 h to analyze their ocular tissues and plasma. The concentrations of NVCM in the conjunctiva, cornea, aqueous humour, iris, ciliary body and plasma were measured by HPLC with photodiode array detector. The pharmacokinetic parameters were calculated by Kinetica 5.1. RESULTS: The highest concentrations of NVCM for the CTOIDD group and control group were 2105.45±919.89 µg/g and 97.18±43.14 µg/g in cornea, 3033.92±1061.95 µg/g and 806.99±563.02 µg/g in conjunctiva, 1570.19±402.87 µg/g and 46.93±23.46 µg/g in iris, 181.94±47.11 µg/g and 15.38±4.00 µg/g in ciliary body, 29.78±4.90 µg/mL and 3.20±1.48 µg/mL in aqueous humour, and 26.89±5.57 µg/mL and 1.90±1.87 µg/mL in plasma, respectively. The mean NVCM levels significantly increased at all time-points in cornea, iris, and ciliary body (p<0.05) in the CTOIDD group. The AUC0-24 values in the CTOIDD group were 27,543.70 µg·h/g in cornea, 32,514.48 µg·h/g in conjunctiva, 8631.05 µg·h/g in iris, 2194.36 µg·h/g in ciliary body and 343.9 µg·h/mL in aqueous humour, which were higher than for the eye drop group in all tissues. CONCLUSION: Since continuous instillation of NVCM with CTOIDD could reach significantly higher concentrations and was sustained for a longer period compared with hourly administration of eye drop, CTOIDD administered NVCM could be a possible method to treat bacterial keratitis.

Sub-Tenon Sustained Controllable Delivery of Dexamethasone for Treating Severe Acute Experimental Uveitis.

PURPOSE: To evaluate the efficacy of dexamethasone (DXM) through sub-tenon sustained controllable drug delivery system (SSCDDS) for treating severe acute experimental uveitis. METHODS: Rabbits were treated with either DXM (treated group) or normal saline (control group) through SSCDDS. Clinical signs of uveitis were assessed at days 1, 3, 5, 7, and 14 after treatment. Histopathologic examinations were performed to evaluate inflammatory cell infiltration on posttreatment days 7 and 14. RESULTS: All signs of experimental uveitis were reduced by SSCDDS of DXM according to clinical criteria, and the treated group had significantly less inflammation than the control group (p<0.05). Histopathologic examinations showed severe inflammation and marked inflammatory cell infiltration in the control group, but minimal inflammation in the treated group. CONCLUSIONS: Sub-tenon sustained controllable delivery of DXM effectively suppresses severe acute inflammation in a rabbit model of uveitis. The proposed minimal invasive system might be a promising candidate for managing severe ocular diseases.

Exploring differentially expressed key genes related to development of follicle by RNA-seq in Peking ducks (Anas Platyrhynchos).

Duck follicles enter different reproductive phases throughout life, and follicle gene expression patterns differ according to these phases. In particular, differentially expressed genes and related to development of follicle (mRNAs) play an important role to explore the key genes in this process; however, the expression profiles of these genes remain unclear. In this study, transcriptome sequencing was used to investigate the expression levels of duck ovarian genes, and comparative transcriptional analysis was carried out to identify differential genes, and cluster them into groups and function identification. The results showed differential expression of 593 coding genes between young and laying ducks, and of 518 coding genes between laying and old ducks. In further GO analysis, 35 genes from the comparison between old ducks and laying ducks have significant been changed involved in hormones related to follicle development. They include up-regulated genes StAR, CYP17, EPOX, 3ß-HSD, CYP1B1 CYP19A1 and down-regulated genes SR-B1 in laying ducks hormone synthesis than old ducks. Among which EPOX is a key gene for time special highly expression during egg laying stage, and other key regulatory genes' highly expression showed in young and laying stage, and lower expression showing with follicular development stopping. Therefore, EPOX is a key regulator for duck follicle development in laying period, its expression level increase 100 times higher than in youth and decrease 98% than stop laying period in duck life cycle.

Identification of aberrantly methylated differentially expressed genes in age-related macular degeneration.

DNA methylation plays a significant role in many diseases. Age-related macular degeneration (AMD) is a leading cause of vision loss for people aged 50 years and above, but the etiology and pathogenesis are largely unknown. This study aimed to identify the aberrantly methylated differentially expressed genes (DEGs) in AMD and predict the related pathways on the basis of public data.Aberrant methylation can influence the functions of key genes by altering their expression. Here, we found out DEGs by overlapping public microarray data (GSE29801 and GSE102952). Functional and enrichment analyses of selected genes were performed using the DAVID database. Subsequently, protein-protein interaction (PPI) networks were constructed by using STRING and visualized in cytoscape to determine hub genes. Finally, we collected AMD patients' blood samples to identify the methylation statuses of these hub genes by using methylated DNA immunoprecipitation.In total, 156 hypermethylation-low expression genes and 127 hypomethylation-high expression genes were predicted. The hypermethylation-low expression genes were enriched in biological processes of response to cardiac conduction, ATP binding, and cell-cell junction assembly. The top 5 hub genes of the PPI network were HSP90AA1, HSPA1L, HSPE1, HSP90B1, and NOP56. Meanwhile, the hypomethylation-high expression genes were enriched in the biological processes of response to positive regulation of the MAPK cascade, actin cytoskeleton reorganization, dentate gyrus development, and cell migration. The top 5 hub genes of this PPI network were PIK3R1, EZR, IGF2, SLC2A1, and CDKN1C. Moreover, the methylation statuses of NOP56, EZR, IGF2, SLC2A1, CDKN1C were confirmed to be altered in the blood of AMD patients.This study indicated possible aberrantly methylated DEGs and differentially expressed pathways in AMD by bioinformatics analysis, providing novel insights for unraveling the pathogenesis of AMD. Hub genes, including NOP56, EZR, IGF2, SLC2A1, CDKN1C, might serve as aberrant methylation-based candidate biomarkers for AMD in future applications.

Thermally triggered injectable chitosan/silk fibroin/bioactive glass nanoparticle hydrogels for in-situ bone formation in rat calvarial bone defects.

Copper-containing bioactive glass nanoparticles (Cu-BG NPs) with designed compositions and sizes were synthesized and incorporated into chitosan (CH)/silk fibroin (SF)/glycerophosphate (GP) composites to prepare injectable hydrogels for cell-free bone repair. The resulting Cu-BG/CH/SF/GP gels were found to exhibit well-defined injectability and to undergo rapid gelation at physiological temperature and pH. They were highly porous and showed the ability to administer Si, Ca and Cu ions at their respective safe doses in a sustained and controlled manner. In vitro studies revealed that the gels supported the growth of seeded MC3T3-E1 and human umbilical vein endothelial cells, and effectively induced them toward osteogenesis and angiogenesis, respectively. In vivo bone repair based on a critical-size rat calvarial bone defect model demonstrated that the optimal Cu-BG/CH/SF/GP gel was able to fully restore the bone defect with formation of vascularized bone tissue and mineralized collagen deposition during a treatment period of 8 weeks without utilization of any cells and/or growth factors. The results suggest that the presently developed Cu-BG/CH/SF/GP composite hydrogels have great potential and translation ability for bone regeneration owing to their thermo-sensitive properties, cell-free bioactivity, and cost-effectiveness. STATEMENT OF SIGNIFICANCE: Hydrogels loaded with cells and/or growth factors exhibit potential in bone repair. However, they have been facing obstacles related to the clinic translation. Here, a novel type of hydrogel system consisting of copper-containing bioactive glass nanoparticles and chitosan/silk fibroin composite was developed. These gels showed injectability and thermally triggered in situ gelation properties and were able to administer the release of ions at safe but effective doses in a controlled manner while inducing the seeded cells toward osteogenesis and angiogenesis. The optimal gel showed the ability to fully repair critical-size rat calvarial bone defects without involving time consuming cell processing and/or the use of expensive growth factors, confirming that this novel hydrogel system has great potential for translation to the clinic.

Potentiating photodynamic therapy of ICG-loaded nanoparticles by depleting GSH with PEITC.

Photodynamic therapy (PDT) is a clinically approved cancer treatment which utilizes reactive oxygen species (ROS) to eradicate cancer cells. But the high concentration of GSH inside tumor cells can neutralize the generated ROS during PDT, resulting in an insufficient therapeutic effect. To address this issue, we combined ICG-loaded nanoparticles with PEITC for potent PDT. ICG encapsulated in novel hydroxyethyl starch-oleic acid conjugate (HES-OA) nanoparticles (∼50 nm) exhibited excellent stability and efficient singlet oxygen generation under laser irradiation, promoted cellular uptake, and enhanced tumor accumulation, whilst PEITC depleted intracellular GSH significantly. As a result, PDT based on ICG-loaded NPs combined with PEITC synergistically suppressed cancer cells both in vitro and in vivo. Potentiating ICG-loaded NPs with PEITC represents a novel and efficient strategy to enhance PDT efficacy.

Total glucosides of paeony suppresses experimental autoimmune uveitis in association with inhibition of Th1 and Th2 cell function in mice.

Total glucosides of paeony (TGP) are active components extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the role and mechanisms of TGP in experimental autoimmune uveitis (EAU) model of mice. The C57BL/6 mice were randomly divided into three groups: sham group, EAU-control group, and EAU-TGP group. Clinical score of images of the eye fundus were taken on 7, 14, 21, and 28 days after induction of EAU. The concentrations of proinflammatory cytokines in intraocular fluid were measured at 14 days after EAU induction with the use of a multiplex assay system. Flow cytometry was used to analyze the frequency of CD4+, CD8+, interferon-gamma (IFN-γ), and CD4+/CD8+ ratio in spleen and lymph nodes. Western blotting was used to measure expressions of mitogen-activated protein kinase (MAPK) pathway-related proteins in retina. Clinical scores for uveitis were lower in TGP-treated EAU mice than those without TGP treatment. Importantly, the concentrations of cytokines induced by T-helper 1 (Th1) and T-helper 2 (Th2) cells in intraocular fluid were reduced in EAU mice treated with TGP. Furthermore, the frequency of CD4+, IFN-γ, and CD4+/CD8+ ratio was decreased and the frequency of CD8+ was increased in spleen and lymph nodes of mice treated with TGP. The anti-inflammatory effects of TGP were mediated by inhibiting the MAPK signaling pathways. Our results showed that TGP suppressed uveitis in mice via the inhibition of Th1 and Th2 cell function. Thus, TGP may be a promising therapeutic strategy for uveitis, as well as other ocular inflammatory diseases.

iRGD-decorated reduction-responsive nanoclusters for targeted drug delivery.

Herein, reduction-responsive disintegratable nanoclusters (NCs) were prepared as a novel nanovehicle for targeted drug delivery. The NCs, with a diameter of ∼170 nm, were self-assembled from hydrophobically modified and iRGD decorated hydroxyethyl starch (iRGD-HES-SS-C18). DOX was loaded into the NCs as a model drug. DOX@iRGD-HES-SS-C18 NCs can disintegrate into smaller ones and release DOX under reduction stimuli. Due to the ligand-receptor binding interactions between iRGD and integrin αV, DOX@iRGD-HES-SS-C18 NCs can specifically bind to the cell membranes of HepG-2 and 4T1 cells (integrin αV positive), resulting in enhanced cellular uptake as compared to DOX@HES-SS-C18 NCs. After cellular internalization, the NCs were transported to endosomes/lysosomes in which the reductive environment triggered the disintegration and DOX release. As a consequence, DOX@iRGD-HES-SS-C18 NCs exhibited an enhanced antitumor effect as compared to DOX@HES-SS-C18 NCs and free DOX, in an in vitro antitumor activity study. The reduction-responsive disintegratable NCs reported here were proved to be a safe and efficient nanoplatform, holding significant translation potential for tumor-targeted drug delivery.

Preliminary study of a controllable device for subtenon drug infusion in a rabbit model.

BACKGROUND AND OBJECTIVE: Conventional methods to treat intraocular diseases are invasive or associated with adverse effects. A minimally invasive means of sustained-release drug delivery to the vitreous is required. This study evaluated a novel device for subtenon drug delivery to the vitreous, relative to a single subconjunctival injection. METHODS: Sixty adult New Zealand White rabbits were randomly assigned to receive demethylvancomycin (DMV) by continuous subtenon delivery with the flow rate of 0.1 ml/hr for 24 hr, or as a single 0.3 ml subconjunctival injection in the right eyes. Rabbits were killed in subgroups of six at 1, 3, 6, 12 and 24 hr. The DMV concentration of the vitreous humour of the right eye was analysed by high-performance liquid chromatography. RESULTS: Overall, the vitreous DMV concentration of the subtenon group was significantly higher than that of the subconjunctival group (F = 25.928, p = 0.001). The DMV concentration of the subtenon group was also significantly higher than that of the subconjunctival group at 3, 6, 12 and 24 hr (t = 2.457, 5.064, 3.085, 4.207; p = 0.04, 0.01, 0.018, 0.004, respectively). In the subtenon group, the DMV concentration reached maximum (2.41 ± 0.67 µg/ml) at 6 hr, and at 24 hr was 2.37 ± 1.23 µg/ml. In the subconjunctival group, the DMV concentration reached maximum (0.48 ± 0.27 µg/ml) at 1 hr and declined to 0.09 ± 0.05 µg/ml at 24 hr. CONCLUSION: Subtenon application with this novel minimally invasive design is an effective method for delivering an appropriate drug to the vitreous in a sustained and controllable amount.

Opacification of a Hydrophilic Acrylic Intraocular Lens.

Opacification of a hydrophilic acrylic intraocular (IOL) lens is a rare phenomenon. We herein report a case of a 57-year man complaining of decreased vision at left eye for the last 4 months. He had undergone phacoemulsification with IOL implantation 2 years back. IOL opacification was observed through slit-lamp. IOL exchange was carried out. The exchanged IOL and a new lens of the same model were sent to laboratory for pathologic analysis. Confocal microscopy showed uniformly distributed granules from the surface to 80 µm internal surface. Scanning electron microscopy (SEM) showed the details of granules. X-ray photoelectron spectroscopy (XPS) confirmed the presence of calcium and silicon in the deposits. Aqueous humor biochemical analysis revealed a normal result. We discuss the possible causes of opacification of IOL in this report.

Controllable continuous sub-tenon drug delivery of dexamethasone disodium phosphate to ocular posterior segment in rabbit.

Corticosteroids have been used for treatment of posterior segment eye diseases, but the delivery of drug to the posterior segments is still a problem to resolve. In our study, we explore the feasibility of Sub-tenon's Controllable Continuous Drug Delivery to ocular posterior segment. Controllable continuous sub-tenon drug delivery (CCSDD) system, intravenous injections (IV) and sub-conjunctival injections (SC) were used to deliver dexamethasone disodium phosphate (DEXP) in rabbits, the dexamethasone concentration was measured in the ocular posterior segment tissue by Shimadzu LC-MS 2010 system at different time points in 24 h after first dose injection. Levels of dexamethasone were significantly higher at 12, 24 h in CCSDD than two other approaches, and at 3, 6 h in CCSDD than IV in vitreous body (p < 0.01); at 6, 12, 24 h in CCSDD than two other approaches, and at 1, 3 h in CCSDD than IV in retinal/choroidal compound (p < 0.01); at 3, 6, 12, 24 h in CCSDD than two other approaches, and at 1 h in CCSDD than IV in sclera (p < 0.05). The AUC0-24 in CCSDD group is higher than two other groups in all ocular posterior segment tissue. Our results demonstrated that dexamethasone concentration could be sustained moderately higher in the posterior segment by CCSDD than SC and IV, indicating that CCSDD might be a therapeutic alternative to treat a variety of intractable posterior segment diseases.

Research on the comparison of the demethylvancomycin's diffusion-deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection.

PURPOSE: To compare the demethylvancomycin's diffusion-deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection. METHOD: Sixty adult white rabbits were randomly assigned to the subtenon drug delivery group and the subconjunctival injection group. The subtenon drug delivery group was continuously infused demethylvancomycin to the subtenon of rabbits. The subconjunctival injection group was injected demethylvancomycin to the subconjunctival of rabbits. Cornea, iris and sclera were collected for high-performance liquid chromatography analyses to determine drug concentrations at one hour, three hours, six hours, 12 h and 24 h of drug administration. WinNonlin 6.3 was used to calculate the parameters of cumulative area under the curve (AUCcum) of demethylvancomycin. RESULTS: The peak levels of demethylvancomycin concentration of the subtenon drug delivery group and the subconjunctival injection group were 92.406 ± 21.555 and 51.778 ± 14.001 µg/g in cornea, 28.451 ± 10.229 µg/g and 42.271 ± 27.291 µg/g in iris, 153.166 ± 51.738 µg/g and 57.423 ± 18.480 µg/g in sclera. The differences of concentrations between the two groups in cornea and sclera were statistically significant (F = 487.775, p < 0.001; F = 132.748, p < 0.001). The difference in iris was not statistically significant (F = 4.848, p = 0.064). The maximum of AUCcum of the subtenon drug delivery group and the subconjunctival injection group was 1808.23 h * µg/g and 273.73 h * µg/g in cornea, 489.12 h * µg/g and 216.16 h * µg/g in iris and 2166.34 h * µg/g and 392.57 h * µg/g in sclera at 24 h of drug administration. CONCLUSION: The sustained subtenon drug delivery had a better drug permeability and accumulation in the intraocular solid tissue compared to subconjunctival injection, which demonstrated it was probably a promising and effective approach for treating posterior segment diseases and endophthalmitis.

Homocysteine in retinal artery occlusive disease: A meta-analysis of cohort studies.

Few studies have reported the relationship between retinal artery occlusion (RAO) and plasma homocysteine (Hcy) levels. Our goal was to evaluate the association between the plasma Hcy level and the risk of RAO disease. Several databases were searched for all published studies that involved Hcy and RAO. Six studies evaluated hyperhomocysteinemia (hHcy) in retinal artery occlusion patients and controls; the incidence of hHcy in patients with RAO was higher than the control and the pooled odds ratio (OR) was 6.64 (95% confidence interval (CI): 3.42, 12.89). Subgroup analyses showed that the ORs were 4.77 (95% CI: 2.69, 8.46) in Western countries, 22.19 (95% CI: 2.46, 200.37) in Asian countries, 9.70 (95% CI: 4.43, 21.20) in the age matched group, 11.41 (95% CI: 3.32, 39.18) in the sex matched group, 9.70 (95% CI: 4.37, 21.53) in the healthy control group, and 6.82 (95% CI: 4.19, 11.10) in the sample size >30. The mean plasma Hcy level from 5 case-control studies was higher than controls, and the weighted mean difference (WMD) was 6.54 (95% CI: 2.79, 10.29). Retinal artery occlusion is associated with elevated plasma Hcy levels. Our study results suggest that hHcy is probably an independent risk factor for RAO.