Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice.

PURPOSE: This study aimed to analyse shifts in renin-angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice. METHODS: Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses. RESULTS: Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p < 0.001) and significantly lower body weights (p < 0.001). Colour photography and FFA did not reveal any vessel abnormalities in the diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2+ pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice. CONCLUSIONS: Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

Influence of super-hydrophobic silicone rubber substrate on the growth and differentiation of human lens epithelial cells.

Materials with low cell adhesion are advantageous for production of replacement intraocular lens (IOL) to prevent posterior capsular opacification (PCO). We evaluated the feasibility of compression molding for manufacture of silicone rubber with super-hydrophobic surface and low cell infiltrative characteristics compared to ordinary hydrophobic silicone rubber. Silicone specimens with complex surface topology (super-hydrophobic) or smooth surfaces (hydrophobic) were manufactured by vacuum deforming and molding. Contact angle, microscopic surface structure, and transparency were evaluated. Super-hydrophobic and smooth samples were compared for effects on proliferation, adhesion, and morphology of human lens epithelial cells (hLECs). Epithelial-mesenchymal transition (EMT) was examined by immunofluorescence expression of fibronectin (Fn), Alpha-smooth muscle actin (α-SMA), and vimentin. The surface contact angle of super-hydrophobic silicone was greater than that of smooth silicone (153.8° vs. 116°). The super-hydrophobic surface exhibited a micron-scale palisade structure under scanning electron microscopy (unit length, width, and height of 80, 25, and 25 µm, respectively). However, cell number per 50 × microscopic field on super-hydrophobic surfaces was markedly reduced 24 and 72 h post-seeding compared to smooth surfaces (p < 0.01). Cells were cuboidal or spherical after 72h on super-hydrophobic surfaces, and exhibited numerous surface microvilli with fluff-base polarity, while cells on smooth surfaces exhibited morphological characteristics of EMT. Expression levels of the α-SMA and vimentin were reduced on super-hydrophobic surfaces compared to smooth surfaces. Super-hydrophobic silicon inhibits proliferation, adhesion, and EMT of hLECs, properties that may prevent fibrosis following cataract surgery.

RISK OF SILICONE OIL AS VITREOUS TAMPONADE IN PARS PLANA VITRECTOMY: A Systematic Review and Meta-Analysis.

PURPOSE: The authors examined the differences between silicone oil and other vitreous tamponades or placebo in performing pars plana vitrectomy. METHODS: This review and meta-analysis was conducted in accordance with the PRISMA guidelines. Seven databases and the reference lists of the retrieved randomized controlled trial articles were searched to identify eligible studies. The primary outcomes were the rate of redetachment after endotamponade removal, the rate of reoperation, and poor visual acuity. The secondary outcomes were adverse events and quality of life related to postoperative position. RESULTS: Ten articles (12 trials) were included. There were no significant differences between silicone oil and other agents in most of the primary and second outcomes. Only the risk of hypotony was found to be significantly lower when filling with silicone oil, compared with other agents. No trial reported the quality of life related to postoperative position. CONCLUSION: Based on the available studies, the authors conclude that there is no significant difference in the risk of poor outcomes between pars plana vitrectomy with silicone oil and that with other vitreous tamponades with different surgical histories.

Retinal vessel oxygen saturation and vessel diameter in retinitis pigmentosa at various ages.

PURPOSE: This study was conducted to determine whether oxygen saturation and retinal blood vessel diameter are affected by retinitis pigmentosa (RP) at various ages. METHODS: Relative oxygen saturation was measured in retinal blood vessels in 68 RP patients and 136 normal subjects using the Oxymap T1 retinal oximeter. Subjects were divided into two age groups: Group A (20-40 years) and Group B (> 40 years). One randomly selected eye of each subject was used for statistical analysis. Student's t tests were used to analyze the mean saturation and diameter of retinal arterioles and venules and arteriovenous differences between RP and normal subjects in the two age groups. A Spearman test was used to analyze the correlation of mean saturation of retinal arterioles (AS) and arteriovenous differences (AVS) with visual acuity, disease duration, and electroretinogram (ERG) b-wave amplitude in patients with RP. RESULTS: AS was significantly higher in patients with RP (105.5 ± 9.4 %) than in normal subjects (94.5 ± 4.4 %, p = 0.000) in Group A, while in Group B, AS was significantly lower in RP patients (86.8 ± 10.3 %) than in healthy subjects (96.0 ± 4.8 %, p = 0.000). Vessel diameter was smaller in RP patients than in normal subjects. AS and AVS showed a negative correlation with disease duration and a tendency toward positive correlation with ERG b-wave in patients with RP. CONCLUSIONS: The shifting characteristics of retinal vessel oxygen saturation suggest that the pathological mechanism of retinal oxygen metabolic disorder differs by age in patients with RP.

MACULAR BUCKLING USING A THREE-ARMED SILICONE CAPSULE FOR FOVEOSCHISIS ASSOCIATED WITH HIGH MYOPIA.

PURPOSE: To investigate the safety and efficacy of a novel macular buckling technique on foveoschisis in highly myopic eyes. METHODS: Highly myopic eyes with foveoschisis, posterior staphyloma, and axial length greater than 26.5 mm, but without a full-thickness macular hole, were included. Macular buckling was performed in the included eyes using a three-armed adjustable silicon capsule. RESULTS: Eight eyes from eight patients (five women) were enrolled in this study. The mean follow-up period was 11.6 (range 9-14) months. After surgery, the best-corrected visual acuity was improved in 7/8 (87.5%) eyes, optical coherence tomography imaging showed gradual anatomic improvement of macula over time. The final best-corrected visual acuity gained 21.5 early treatment diabetes retinopathy study letters from baseline on average (P = 0.014). Postoperatively, the most common complications were transiently elevated intraocular pressure (62.5%) and asymptomatic abduction limitation (100%), and the most serious complication was hemorrhagic choroidal detachment (25%). CONCLUSION: Macular buckling with a three-armed adjustable silicone capsule resulted in anatomic and visual improvement in eyes with myopic foveoschisis.

Shifts in retinal vessel diameter and oxygen saturation in Chinese type 2 diabetes mellitus patients.

BACKGROUND: The aim of this study was to analyze the shifts in retinal vessel diameter and oxygen saturation in diabetic patients with and without diabetic retinopathy (DR), as well as to assess the association between diabetes duration and either vessel diameter or oxygen saturation. METHODS: In total, 99 Type 2 DM patients were recruited for the study and were divided into three groups: DM with non-obvious retinopathy (DM, n = 29), non-proliferative diabetic retinopathy (NPDR, n = 40), and proliferative diabetic retinopathy (PDR, n = 30). In addition, 78 age-matched healthy individuals were chosen as the control. The diameter and oxygen saturation of the retinal vessels were analyzed using a noninvasive retinal oximeter, and then compared between the three groups and the normal control. Association analysis was applied to analyze the possible influencing factors, including the diameter and oxygen saturation of retinal vessels, on best corrected visual acuity BCVA, as well as the relationship between diabetes duration and the oximetry values. RESULTS: All of the diabetic patients showed thinner arterioles, wider venules, and a smaller arteriolar-to-venular ratio (AVR) than the healthy individuals. The AVR results from the controls through to the PDR group were 0.81 ± 0.07, 0.78 ± 0.07, 0.76 ± 0.07 and 0.67 ± 0.07, respectively. Both the NPDR and PDR groups showed significantly smaller AVR than the control. All of the diabetic patients exhibited higher retinal vessel oxygen saturation than the healthy individuals. Among all of the oximetry values, AVR exhibited the most significant correlation with best corrected visual acuity (BCVA) (ß = 1.533, P < 0.0001). An increased diabetes duration was associated with decreased arteriolar diameter (slope = -0.082 pixels/year, r (2) = 0.085, P = 0.004) and AVR (slope = -0.009/year, r (2) = 0.349, P < 0.001), and with increased venular diameter (slope = 0.104 pixels/year, r (2) = -0.109, P = 0.001). CONCLUSIONS: In this Chinese population with type 2 DM, the thinner arterioles and wider venules point to microvascular dysfunction in DR. The increased oxygen saturation of the retinal vessels suggests that retinal oxygen metabolism is affected in diabetic retinopathy.

Retinal vessel oxygen saturation and vessel diameter in high myopia.

PURPOSE: To investigate changes in retinal vessel oxygen saturation and diameter in high myopia. METHODS: Relative oxygen saturation was measured in the retinal blood vessels of 54 participants with high myopia and compared to a control group of 54 individuals with emmetropia with the Oxymap T1 retinal oximeter. The participants with high myopia were further divided into two groups according to the grade of myopic retinopathy: Group A (grade < M2 ) and Group B (grade ≥ M2 ). One-way anova was used to analyse the mean saturation and diameter of retinal arterioles and venules and the mean difference in arterio-venous saturation among the four groups. Further analysis of multiple comparisons was performed with the Bonferroni test. Linear regression was used to analyse the correlation of ocular perfusion pressure or best corrected visual acuity with other variables. RESULTS: For all of the high myopia patients, retinal arteriole saturation (92.3 ± 5.6%) and the difference in arterio-venous saturation (30.8 ± 5.0%) were significantly lower than in normal individuals (96.0 ± 5.8%, 35.4 ± 6.2%; p = 0.006, p < 0.001, respectively). In Group A, only the difference in arterio-venous saturation (31.0 ± 4.7%) was significantly lower than in the control group (p = 0.011). In Group B, retinal arteriole saturation (92.2 ± 5.3%) and the difference in arterio-venous saturation (30.7 ± 5.3%) were also lower than the control group (p = 0.02, p = 0.001, respectively). Both retinal arteriole diameter and retinal venule diameter were narrower than in participants with high myopia than the control group (p < 0.001). No statistically significant correlations were found between ocular perfusion pressure or best corrected visual acuity with any other variables. CONCLUSIONS: The study demonstrated decreased retinal arteriole saturation and decreased difference in arterio-venous saturation as well as narrowing retinal vessel diameter in highly myopic eyes. Further studies are needed to determine if such changes play a role in the development of high myopia and its complications or occur as a consequence of tissue remodelling during axial elongation.

Ocular pathogenesis and immune reaction after intravitreal dispase injection in mice.

PURPOSE: The purpose of the current study was to examine the ocular pathogenesis and immune reaction in mice after intravitreal dispase injection. METHODS: Three microliters of dispase at a concentration of 0.2 U/µl were injected into the vitreal cavities of 4-6-week-old mice. Hematoxylin and eosin staining, immunofluorescence analysis, and electroretinograms of the eyes were then performed to assess ocular changes, and enzyme-linked immunospot assays and intracellular staining of single-cell suspensions of the spleens were used to detect immune changes during an 8 week observation period. RESULTS: Neutrophils were the main inflammatory infiltrating cells appearing at the anterior chamber. No cluster of differentiation (CD)3+ labeled T cells, F4/80+ labeled macrophages, or CD56+ labeled natural killer cells were found in the vitreal cavities or retinas in dispase-injected mice within 5 days after injection. Proliferative vitreoretinopathy (PVR)-like signs first appeared at 2 weeks, gradually increased thereafter, and reached peak values at 8 weeks. There was a statistically significant difference in b-wave amplitudes between the PVR and saline-control eyes. Enzyme-linked immunospot assays and intracellular staining showed that specific CD4+ and CD8+ labeled T cells were not involved in dispase-injected mice. CONCLUSIONS: Our data show that neutrophils in the anterior chamber and PVR-like signs in the retinas were found, and that specific immune reactions were not involved after intravitreal dispase injection in mice.

Evaluation of 5-fluorouracil released from a foldable capsular vitreous body in vitro and in vivo.

BACKGROUND: Previously, we have confirmed that the foldable capsular vitreous body (FCVB) can serve as a drug delivery system (DDS) as well as a vitreous substitute. Here, we evaluated the characteristics of the release of 5-fluorouracil (5-Fu) from FCVB in vitro and in vivo. METHODS: For the in-vitro study, various concentrations of 5-FU (50-200 µg/ml) were injected into FCVB capsules and immersed in cups of modified Franz diffusion cells, and liquid was aspirated at specific time intervals. In the in-vivo study, FCVB was folded and implanted into the vitreous cavity in the right eyes of five rabbits, and then 1.0 ml 5-Fu (200 µg/ml) was injected into the capsule. Another five rabbits that were used as the controls received intravitreal injections Aqueous humor was aspirated postoperatively at specific time intervals up to 56 days. The 5-Fu contents in vitro were detected by UV spectrophotometry and ultra performance liquid chromatography (UPLC), and the in-vivo 5-FU levels in the aqueous humour were detected by UPLC. The stock solution in the FCVB before-release study and the FCVB residue were collected for UPLC analysis. RESULTS: UV spectrophotometry revealed that 5-FU was released from FCVB in vitro in a time-dependent manner from 20-360 min in vitro. UPLC analysis revealed that 5-FU was released sustainably from FCVB. The 5-FU concentration in the aqueous humour was detected until postoperative day 56 (D56), with sustained release from postoperative days 3-56. However, the 5-FU concentration in the control samples was detected until only D7, and could not be detected on D14. Finally, 48.8% of the 5-FU was released on D56 in the in-vivo experiment. CONCLUSIONS: FCVB can release 5-Fu sustainably and mechanically, indicating that FCVB can be used as a common vehicle for the sustainable release of different drugs. FCVB is a potentially valuable pharmaceutical adjunct to conventional vitreous surgery for managing or preventing proliferative vitreoretinopathy.

Preliminary efficacy and safety of a silicone oil-filled foldable capsular vitreous body in the treatment of severe retinal detachment.

PURPOSE: We previously invented a novel foldable capsular vitreous body (FCVB) in the treatment of severe retinal detachment. The purpose of this study was to determine its hydrolytic stability in vitro and further evaluate its efficacy and safety in human eyes. METHODS: The hydrolytic stability test proceeded according to State Food and Drug Administration guidelines about intraocular lenses of the ophthalmic implants. A standard three-port pars plana vitrectomy was performed, and FCVB was triple folded and sent into the vitreous cavity of three eyes; then silicone oil was injected into the capsule to support the retina. The treated eyes were examined using Goldmann applanation tonometry, fundus photography, optical coherence tomography, noncontact specular microscopy, and ultrasound biomicroscopy during a 12-month follow-up appointment. RESULTS: The mass of FCVB with silicone oil after 60-day accelerating aging temperature was equal to that at baseline. The FCVB can easily be implanted into the vitreous cavity through a 3-mm incision. The visual acuity and intraocular pressure after FCVB implantation show a slight elevation compared with those of preoperative eyes. The fundus and optical coherence tomography showed that the FCVB was well distributed in the vitreous cavity and evenly supported the retina. Retinal reattachment was found in 3 eyes at the 12-month examination. There was no statistically significant decrease in the density of corneal endothelial cells from baseline to 12 months after FCVB implantation. Ultrasound biomicroscopy showed that the FCVB smoothly contacted but not crushed the ciliary body. CONCLUSION: Silicone oil-filled FCVB was shown to be effective and safe in 3 eyes as a vitreous substitute over a 12-month observation time.

Biocompatibility and retinal support of a foldable capsular vitreous body injected with saline or silicone oil implanted in rabbit eyes.

INTRODUCTION: The aim of this study was to evaluate over a 180-day period the biocompatibility and retinal support of a foldable capsular vitreous body injected with either saline or silicone oil implanted in rabbit eyes. METHODS: A standard three-port pars plana vitrectomy was performed, and foldable capsular vitreous bodies were implanted into the vitreous cavity of rabbit eyes (n = 18). Silicone oil tamponade was used as the control group (n = 5). Of the foldable capsular vitreous body-implanted eyes, either saline (n = 9) or silicone oil (n = 9) was injected into the foldable capsular vitreous body to support the retina. The treated eyes were examined using a slit lamp with a non-contact slit-lamp lens, a tonopen, a non-contact specular microscope and a B-scan ultrasound during the 180-day implantation period. A histological examination was performed at 90 and 180 days. RESULTS: During the 180-day implantation period, no significant corneal keratopathy or intraocular inflammation was noted, and the intraocular pressure (IOP) and corneal endothelial numbers remained steady among the three groups. B-scan ultrasonography showed a smoothly increased echogenicity in front of the retina in group of foldable capsular vitreous bodies injected with saline. Gross examination showed that the foldable capsular vitreous bodies injected with saline or silicone oil smoothly supported the retina. The saline or silicone oil inside the foldable capsular vitreous body was homogeneous, transparent and filled the foldable capsular vitreous body. Histological examination showed no obvious abnormality of the cornea, ciliary body or retina in the foldable capsular vitreous body-implanted eyes. CONCLUSIONS: These results suggest that foldable capsular vitreous bodies injected with either saline or silicone oil showed good biocompatibility and retinal support in rabbit eyes over a 180-day implantation time.

Vitreous function and intervention of it with vitrectomy and other modalities.

The vitreous body, the largest intraocular component, plays a key role in eye development, refraction, cell barrier function, oxygen metabolism and the pathogenesis of assorted diseases. Age, refraction and systemic diseases can cause vitreous metabolic abnormalities. With the continuous development of vitrectomy techniques and equipment, vitreous injections and vitrectomies have increased over the recent decades. However, the normal oxygen tension gradient in the vitreous helps to protect the lens and anterior chamber angle from oxidative stress damage, whereas the increased vitreous oxygen tension around lens and the trabecular meshwork after vitrectomy. It may lead to postoperative nuclear cataract and increase the risk for glaucoma. As a conventional procedure, scleral buckling holds several advantages over vitrectomy in selected cases. This review raises concerns regarding the function of the vitreous and encourages conducting vitreous interventions prudently if it is possible.

Optic nerve head astrocytes contribute to vascular associated effects.

Purpose: This study was conducted in order to test the expression of vasoactive substances within rat lamina cribrosa (LC) and optic nerve head (ONH) astrocytes, so as to investigate the role and potential mechanism of ONH astrocytes in vascular associated effects. Methods: LC tissue sections and primary cultured ONH astrocytes were obtained from adult Sprague-Dawley (SD) rats. Immunofluorescent staining was then used to detect the expression of vasoactive substances. Hyperoxia exposure was carried out both in vivo and in vitro, after which nitric oxide (NO) levels in LC tissue and cell supernatant were detected. The variations of protein and gene expression associated with vasoactive substances were subsequently tested. ONH astrocytes and vascular smooth muscle cells (VSMCs) were then incubated in a direct co-culture manner. Morphological parameters of VSMCs were finally analyzed in order to evaluate cell contraction. Results: Endothelin-1 (ET-1), nitric oxide synthase (NOS) and renin-angiotensin system (RAS) were detected in both LC tissue and ONH astrocytes. Retinal vessel diameter was found obviously decreased following hyperoxia exposure. Moreover, hyperoxia inhibited NO production both in vivo and in vitro. ET-1 and RAS elements were observed to be upregulated, whereas NOS was downregulated. In ONH astrocytes and VSMCs co-culture system, the length-to-width ratio of VSMCs was shown to significantly increase on days 3 and 7 in hyperoxia compared with normoxia. Conclusions: There is an abundance of expression of vasoactive substances within LC tissue and ONH astrocytes. The contractile response of VSMCs in the co-culture system provided direct evidence for the involvement of ONH astrocytes in vascular associated effects, which may signify a potentially novel direction for future research.

TREM-1 amplifies corneal inflammation after Pseudomonas aeruginosa infection by modulating Toll-like receptor signaling and Th1/Th2-type immune responses.

As a novel family of cell surface receptors, triggering receptors expressed on myeloid cells (TREMs) play an important role in inflammatory responses. However, the role of TREMs in the ocular immune system remains unknown. In this study, we examined the expression and function of TREM-1 in Pseudomonas aeruginosa keratitis, one of the most common sight-threatening ocular diseases. TREM-1 was significantly increased in human corneas after P. aeruginosa infection. Consistent with TREM-1 expression at the human ocular surface, TREM-1 levels (mRNA and protein) were also elevated in the infected corneas of C57BL/6 (B6) mice at 1, 3, and 5 days postinfection. To determine whether TREM-1 dictates the outcome of P. aeruginosa keratitis in susceptible mice, TREM-1 signaling in B6 mice was blocked with a soluble mTREM-1/Fc fusion protein. The results indicated that blockade of TREM-1 reduced the severity of corneal disease, polymorphonuclear neutrophil infiltration, Th1/proinflammatory cytokine expression and Toll-like receptor (TLR) activation but enhanced the production of Th2 cytokines, murine ß-defensin 2 (mBD2), single Ig interleukin-1R-related molecule (SIGIRR), and ST2. Furthermore, we also used agonistic anti-mTREM-1 antibody to activate TREM-1 signaling in B6 mice and found that TREM-1 activation resulted in worsened disease and earlier corneal perforation in infected B6 mouse corneas and elevated production of proinflammatory cytokines and TLR signaling molecules but reduced expression of mBD2, SIGIRR, and ST2. To the best of our knowledge, this study provides the first evidence that TREM-1 functions as an inflammatory amplifier in P. aeruginosa keratitis by modulating TLR signaling and Th1/Th2 responses.

E13.5 retinal progenitors induce mouse bone marrow mesenchymal stromal cells to differentiate into retinal progenitor-like cells.

BACKGROUND AIMS: Retinal progenitor cells (RPC) are an excellent resource for retinal replacement therapy but usually unavailable. We attempted to induce bone marrow mesenchymal stromal cells (BMSC) into RPC. METHODS: BMSC and embryonic day 13.5 (E13.5) RPC derived from wild-type or enhanced green fluorescence protein (EGFP) transgenic (Egfp(+/+)) mice were co-cultured in a transwell or re-aggregation system. Gene and protein expressions were investigated by reverse transcription-polymerase chain reaction (PCR) and immunofluorescence, respectively. Spontaneous cell fusion was evaluated by Chloromethylbenzamido derivative of 1,1'- dioctadecyl-3,3,3',3' - tetramethylindocarbocyanine perchlorate (CM-DiI) labeling together with EGFP tracing. RESULTS: BMSC from both wild-type and Egfp(+/+) mice displayed similar spindle shapes. The undifferentiated BMSC already expressed immature neural markers but did not express Nfl, Gfap or the retina-related genes Pax6, Math5 and Brn3b. When co-cultured with E13.5 RPC in the transwell system, BMSC displayed transient expression of early retinal development genes, including Pax6, Math5 and Brn3b at 3 days, as well as long-term expression of Nfl (up to 21 days). No expression of the late photoreceptor gene rhodopsin could be detected at any time. In re-aggregation co-culture, E13.5 RPC induced EGFP-positive BMSC to express not only the early retinal development genes but also the late gene rhodopsin. Furthermore, a small fraction of BMSC could be induced to express the synaptophysin protein. Re-aggregation co-culture of CM-DiI-labeled BMSC and EGFP-positive E13.5 RPC displayed minimal co-localization of the two fluorescence signals. CONCLUSIONS: E13.5 RPC are capable of inducing BMSC towards an RPC fate. The differentiation is independent of cell fusion. Cytokines and cell-cell interactions exert this induction effect, but they have different functions.

Stanniocalcin-1 promotes tumor angiogenesis through up-regulation of VEGF in gastric cancer cells.

BACKGROUND: Stanniocalcin-1(STC-1) is up-regulated in several cancers including gastric cancer. Evidences suggest that STC-1 is associated with carcinogenesis and angiogenic process. However, it is unclear on the exact role for STC-1 in inducing angiogenesis and tumorigeneisis. METHOD: BGC/STC cells (high-expression of STC-1) and BGC/shSTC cells (low- expression of STC-1) were constructed to investigate the effect of STC-1 on the xenograft tumor growth and angiogenesis in vitro and in vivo. ELISA assay was used to detect the expression of vascular endothelial growth factor (VEGF) in the supernatants. Neutralizing antibody was used to inhibit VEGF expression in supernatants. The expression of phosphorylated -PKCßII, phosphorylated -ERK1/2 and phosphorylated -P38 in the BGC treated with STC-1protein was detected by western blot. RESULTS: STC-1 could promote angiogenesis in vitro and in vivo, and the angiogenesis was consistent with VEGF expression in vitro. Inhibition of VEGF expression in supernatants with neutralizing antibody markedly abolished angiogenesis induced by STC-1 in vitro. The process of STC-1-regulated VEGF expression was mediated via PKCßII and ERK1/2. CONCLUSIONS: STC-1 promotes the expression of VEGF depended on the activation of PKCßII and ERK1/2 pathways. VEGF subsequently enhances tumor angiogenesis which in turn promotes the gastric tumor growth.

Vitreous function and intervention of it with vitrectomy and other modalities.

The vitreous body, the largest intraocular component, plays a key role in eye development, refraction, cell barrier function, oxygen metabolism and the pathogenesis of assorted diseases. Age, refraction and systemic diseases can cause vitreous metabolic abnormalities. With the continuous development of vitrectomy techniques and equipment, vitreous injections and vitrectomies have increased over the recent decades. However, the normal oxygen tension gradient in the vitreous helps to protect the lens and anterior chamber angle from oxidative stress damage, whereas the increased vitreous oxygen tension around lens and the trabecular meshwork after vitrectomy may lead to postoperative nuclear cataract and a high incidence of open angle glaucoma. As a conventional procedure, scleral buckling holds several advantages over vitrectomy in selected cases. This review raises concerns regarding the function of the vitreous, and encourages conducting vitreous interventions prudently.

Safety assessment of polymeric micelles as an ophthalmic drug delivery system for intravitreal administration of dasatinib.

BACKGROUND AND AIMS: Ocular safety/biocompatibility is an essential element of ophthalmic drug delivery. We previously applied poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-b-PCL) micelles to deliver dasatinib for the management of proliferative vitreoretinopathy (PVR) in vitro. Herein, we seek to ascertain the ocular safety/compatibility of blank and dasatinib loaded PEG-b-PCL micelles, which will set the stage for the future in vivo efficacy evaluations and/or clinical translation for PVR or other eye diseases. METHODS: To access the safety of blank and dasatinib loaded micelles, in vitro cell based assays (LDH cell membrane damage test, SRB cytotoxicity, TEER and permeability of RPE tight junctions), in vivo slit lamp biomicroscopy and optical coherence tomography, Ex vivo histology (H&E staining, GFAP immunofluorescence staining and TUNEL assay) were undertaken. RESULTS: Both blank and dasatinib loaded micelles showed remarkable safety profiles at cellular levels. They also caused negligible ocular toxicity/abnormalities up to 28 days post-intravitreal injection in mice. The micelles did not insult the cornea, as demonstrated by slit-lamp biomicroscopy. Ex vivo histology and in vivo optical coherence tomography revealed a normal retinal structure with minimal apoptosis and stresses. CONCLUSION: Taken together, both blank and dasatinib loaded micelles appear to be safe and their applications in drug delivery for eye diseases should be explored.

Technical standards of a foldable capsular vitreous body in terms of mechanical, optical, and biocompatible properties.

We previously proposed a new strategy to fabricate a novel foldable capsular vitreous body (FCVB) as a vitreous substitute and found that the FCVB was a very good replacement for closely mimicking the morphology and restoring the physiologic function of the rabbit vitreous body. The aim of this article was to assess the mechanical, optical, and biocompatible properties of a FCVB made from liquid silicone rubber. The mechanical properties show that the shore hardness is 37.80 degrees, the tear strength is 47.14 N/mm, the tensile strength is more than 7.28 MPa, and the elongation ratio is more than 1200%; in addition, the FCVB has 300 nm mili apertures in the capsule. The optical properties reveal that transmittances are 92%, hazes are 5.74%, and spectral transmittance is 97%. The transmittance mission is 2.3% and can sustain a 1500 mW, 0.2 s, 532 nm green laser. The biocompatible properties are shown in the stable extracts experiment, no significant fever, good genetic safety, and no structural abnormality or apoptosis in the cornea, ciliary body, and retina over a 6-month observation period. These results indicate that the FCVB has good mechanical, optical, and biocompatible properties, and the assessment results can be recommended as the FCVB technical standards for industrial manufacturing and inspection.

The Entrepreneur's Psychological Capital, Creative Innovation Behavior, and Enterprise Performance.

In order to analyze the relationship between entrepreneur psychological capital, creative innovation behavior, and enterprise performance based on the actual situation of Chinese enterprises and provide a theoretical basis for the application of entrepreneur psychological capital in enterprise innovation and performance development, in this study, 536 entrepreneurs from 517 enterprises in different fields in Anhui region were selected, and a questionnaire survey on the psychological capital of entrepreneurs, creative innovation behaviors, and corporate performance was conducted. A hypothesis model of the relationship between entrepreneur's psychological capital, creative innovation behavior, and enterprise performance was constructed. The correlation between entrepreneur's psychological capital, creative innovation behavior, and enterprise performance and the intermediation of creative innovation behavior were analyzed using multiple-regression model and structural equation model. The results show that there is a significant positive correlation between dimensions of self-efficacy (regression coefficient = 0.682, p = 0.000), toughness (regression coefficient = 0.526, p = 0.000), and enterprise performance; there is a significant positive correlation between the dimensions of optimism (regression coefficient = 0.471, p = 0.003), hope (regression coefficient = 0.590, p = 0.006), and enterprise performance; there is a significant positive correlation between entrepreneurs' technological innovation behavior (regression coefficient = 0.506, p = 0.000), business innovation behavior (regression coefficient = 0.562, p = 0.000), and enterprise performance; there is a significant positive correlation between entrepreneurial relationship acquisition behavior (regression coefficient = 0.632, p = 0.004) and enterprise performance. Taking entrepreneurs' creative innovation behavior as the intermediary variable, the authors conclude that the dimensions of entrepreneurs' self-efficacy, hope, optimism, toughness, and the standardized path coefficient of enterprise performance are significantly reduced; through the analysis of structural equation model, it is found that the fitting index of the model of entrepreneur's psychological capital, creative innovation behavior, and enterprise performance meets the fitting standard, which shows that both the psychological capital and the creative innovation behavior of entrepreneurs can promote the improvement of enterprise performance. Entrepreneur's creative innovation behavior plays an intermediary effect in the positive influence of entrepreneur's psychological capital on enterprise performance.