Harmol used for the treatment of herpes simplex virus induced keratitis.

Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.

Comparison of early visual quality in patients with moderate myopia using different optical zones in small incision lenticule extraction (SMILE).

BACKGROUND: The early visual qualities of patients with moderate myopia were evaluated after small incision lenticule extraction (SMILE) using different optical zones. METHODS: In this retrospective case study, 27 cases (51 eyes) were selected, including 10 cases in Group A (19 eyes), 6.6-6.8 mm in the optical zone, 10 cases in Group B (19 eyes), 6.4-6.5 mm in the optical zone, and 7 cases in Group C (13 eyes),6.1-6.3 mm in the optical zone. The following items were examined preoperatively and 1 month postoperatively: uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical, cylinder, central corneal thickness (CCT), corneal mean curvature (CMC), total ocular aberrations (TA), total low order aberrations (tLOAs), defocus, astigmatism and total high order aberrations (tHOAs), spherical, coma, trefoil, modulation transfer function (MTF), MTFcutoff, SR, objective scatter index (OSI), point scatter function at 50 and 10% (PSF50%, PSF10%), and contrast visual acuity of 100, 20, and 9% (VA100%, VA20%, and VA9%). We compared the three groups by Kruskal-Wallis test. Wilcoxon signed ranks test was used for each group before and 1 month after surgeries. P< 0.05 was considered statistically significant. RESULTS: There was no significant difference in UCVA, BCVA, CCT, cylinder, and CMC in three groups preoperatively and 1 month postoperatively (P> 0.05). Comparison of the aberrations of the three groups showed statistically significant difference only in TA, tLOA, defocus, astigmatism and SA preoperatively, and trefoil 1 month postoperatively(P< 0.05). The postoperative TA, tLOAs, defocus, astigmatism and trefoil of the three groups were lower than those before surgeries (P< 0.05). The postoperative tHOAs of Group B and C was lower than those before surgeries (P< 0.05). The MTF results showed that before surgeries, there were significant differences in three groups (P< 0.05) in spatial frequencies 5~15 cycles per degree (cpd), and no differences in 20~30 cpd(P> 0.05), while no difference were observed in all spatial frequencies postoperatively (P> 0.05). Comparing the preoperative and postoperative MTF values for each group, the results showed that there was a significant difference in Group C at 5~20 cpd after surgeries(P< 0.05). There was no significant difference in MTFcutoff, SR, OSI, PSF50%, PSF10%, VA100%, VA20%, and VA9% in the three groups preoperatively (P> 0.05). One month after surgeries, higher VA9% values were measured for Group C compared to Group A and B (P < 0.05). There was no significant difference in each group before and after surgeries (P> 0.05). CONCLUSION: SMILE could improve the visual qualities of patients with moderate myopia. Reducing the surgical optical zone will only affect night vision slightly.

Comparison of visual quality after EVO-ICL implantation and SMILE to select the appropriate surgical method for high myopia.

BACKGROUND: This study sought to compare the visual quality between intraocular collamer lens (EVO-ICL) implantation and small-incision lenticule extraction (SMILE) and determine the appropriate surgical method to treat patients with high myopia (- 6.25 to - 10 D). METHODS: A total of 48 eyes underwent EVO-ICL implantation and another 48 eyes underwent SMILE. The uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BCVA) and equivalent spherical degree were compared across the SMILE (- 6.25 to - 10 D) and EVO-ICL (- 6.25 to - 10 D) implantation groups. Preoperative and postoperative visual quality parameters were compared between and within groups. RESULTS: The OQAS II values (OV 100%) one week and one month after surgery and the modulation transfer function (MTF), OV 20% and OV 9% values one week after surgery in the SMILE group were lower than the respective preoperative values. The objective scatter index (OSI) value increased one week as well as one month after surgery compared with the preoperative values. The MTF cut-off value of the SMILE group was lower than that of the EVO-ICL implantation group three months after surgery. CONCLUSIONS: For patients with high myopia, the postoperative visual quality of EVO- ICL implantation was slightly better than that of SMILE.

Comparison of two techniques for toric intraocular lens implantation: hydroimplantation versus ophthalmic viscosurgical devices.

BACKGROUND: To compare the results between hydroimplantation of a single-piece, acrylic foldable toric intraocular lens (IOLs) and conventional implantation using an ophthalmic viscosurgical device (OVD). METHODS: In this study, 60 eyes with cataract and preexisting regular corneal astigmatism of 1.0 to 3.0 diopters (D) underwent the implantation of the AcrySof toric IOLs (Alcon Laboratories, Inc.). The patients were randomly assigned to a conventional implantation technique with an OVD or a hydroimplantation technique. Comparison of preoperative and postoperative parameters was performed using paired Student t tests, and independent Student t test was used to compare between the two groups. RESULTS: Three months postoperatively, the mean subjective astigmatism was 0.45 D ± 0.24 (SD) in the OVD group and 0.49 ± 0.29 D in the hydroimplantation group (P = 0.492). The mean endothelial cell density (ECD) loss was 7.54% ± 0.82% and 7.32% ± 0.59%, respectively (P = 0.117). The mean absolute IOL rotation was 4.77 ± 2.32 degrees and 4.70 ± 1.95 degrees, respectively (P = 0.334). The mean time for IOL implantation was 71.50 ± 8.10 s and 37.60 ± 3.90 s, respectively (P < 0.001). Two hours, 1 day, 1 week, 1 month, and 3 months postoperatively, there was no significant difference in IOP between the two groups (P > 0.05), although IOP two hours postoperatively seemed to be a little higher in the OVD group. CONCLUSIONS: Compared with the use of OVDs for toric IOLs implantation, the hydroimplantation technique provided advantages of increased efficiency, reduced surgical time and cost, and no concerns of OVD-induced elevated IOP. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55696872 , Retrospectively registered (Date of registration: 25 March 2018).

MiR-613 suppresses retinoblastoma cell proliferation, invasion, and tumor formation by targeting E2F5.

Retinoblastoma is a common intraocular malignancy that occurs during childhood. MicroRNAs play critical roles in the regulation of retinoblastoma initiation and progression, and aberrant expression of miR-613 had been reported in various types of cancer. However, the role and mechanism of its function in retinoblastoma are still unclear. In this study, we found that miR-613 was downregulated in retinoblastoma tissues and cell lines. Overexpression of miR-613 suppressed retinoblastoma cell proliferation, migration, and invasion and induced cell cycle arrest in vitro. Additionally, overexpressed miR-613 also inhibited tumor formation of retinoblastoma cells in vivo. We further identified E2F5 as a direct target of miR-613. Reintroduction of E2F5 without 3'-untranslated region reversed the inhibitory effects of miR-613 on cell proliferation and invasion. Our data collectively indicate that miR-613 functions as a tumor suppressor in retinoblastoma through downregulating E2F5, supporting the targeting of the novel miR-613/E2F5 axis as a potentially effective therapeutic approach for retinoblastoma.

Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma.

Histone deacetylase 9 (HDAC9) is a member of class II HDACs, which regulates a wide variety of normal and abnormal physiological functions. Recently, HDAC9 has been found to be overexpressed in some types of human cancers. However, the role of HDAC9 in retinoblastoma remains unclear. In this study, we found that HDAC9 was commonly expressed in retinoblastoma tissues and HDAC9 was overexpressed in prognostically poor retinoblastoma patients. Through knocking down HDAC9 in Y79 and WERI-Rb-1 cells, the expression level of HDAC9 was found to be positively related to cell proliferation in vitro. Further investigation indicated that knockdown HDAC9 could significantly induce cell cycle arrest at G1 phase in retinoblastoma cells. Western blot assay showed downregulation of HDAC9 could significantly decrease cyclin E2 and CDK2 expression. Lastly, xenograft study in nude mice showed that downregulation of HDAC9 inhibited tumor growth and development in vivo. Therefore, our results suggest that HDAC9 could serve as a novel potential therapeutic target in the treatment of retinoblastoma.

Partially hollowed ultra-thin dielectric meta-surface for transmission manipulation.

Impressive optical properties are numerically demonstrated in the partially hollowed dielectric meta-surface (p-HDMS), which consists of an air cavity array intercalated in an ultra-thin (~λ/6) high-index dielectric film. Multispectral transmission band-stop response with near-perfect spectral modulation depth is achieved. The spectral slop is up to 80%/nm, indicating the sharp and narrowband transmission behavior. Classical Malus law is confirmed by this sub-wavelength platform. Moreover, the multispectral light propagation manipulation can be perfectly reproduced by using the actual dielectric with absorption loss. In this all-dielectric meta-surface, conduction loss is avoided compared to its metallic plasmonic counterpart. Such configurations can therefore serve as excellent alternatives for plasmonic meta-surfaces and constitute an important step in nanophotonics.

Can Down-gaze During Near Work Cause Peripheral Deprivation in Asian Eyes?

PURPOSE: We hypothesize that the typically narrower palpebral apertures of East Asian eyes in combination with the narrowing of this aperture during down-gaze combine to reduce light levels and image contrast in the inferior retina during near work, thus creating peripheral deprivation in these eyes that could generate deprivation myopia in children culturally encouraged to perform near work. METHODS: We photographed the right eyes of 53 Chinese children during down-gaze (from 10 to 40 degrees) from the fixation point and the primary gaze position. From these images, we determined the size and shape of the effective foveal and superior field entrance pupil at different down-gaze angles. By using an eye model with typical levels of off-axis higher-order aberrations, we quantified the impact of eyelid and eyelash vignetting of the pupil on both retinal illuminance and image quality using Visual Strehl Ratio (VSOTF), and the non-visually weighted Strehl Ratio (SROTF). RESULTS: The effective aperture for the superior visual field is vignetted during down-gaze by lids and lashes, producing reductions in retinal illuminance of 30% and >60% at 20 and 40 degrees, respectively. However, the aperture vignetting effect on peripheral image modulation is small, with neural and aberration changes dominating image quality in the superior field during down-gaze. CONCLUSIONS: Occlusion of the pupil by eyelid and eyelashes during down-gaze is unlikely to produce significant superior field deprivation in East Asian eyes.

Femtosecond laser-assisted anterior lamellar keratoplasty for the treatment of stromal corneal pathology.

BACKGROUND: To describe the initial outcomes and safety of anterior lamellar keratoplasty (ALK) assisted by a femtosecond laser for stromal corneal pathology. METHODS: A non-comparative case series of 14 eyes (13 patients) with various stromal corneal diseases underwent ALK with a femtosecond laser. Femtosecond laser settings, technique, uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and endothelial cell density (ECD) were measured. RESULTS: All eyes were successfully treated without intraoperative complications. The UCVA improved in 11 eyes (78.6%) compared with preoperative UCVA. The mean difference between preoperative and postoperative UCVA was a gain of 1.7 lines (range, unchanged to 6 lines). The BCVA improved in all eyes compared with preoperative levels. The mean difference between preoperative and postoperative BCVA was a gain of 2.4 lines (range, 1-8 lines). In 3 eyes, phototherapeutic keratectomy was performed. The mean reduction in endothelial cell density was 3.7% after a mean 7.3 months of follow-up. No graft rejection, infection, or epithelial ingrowth was found. CONCLUSIONS: Femtosecond laser-assisted ALK improved UCVA and BCVA in patients with stromal corneal pathology. Our early results indicated that the femtosecond laser produced an effective and smooth dissection through opaque corneas even deeper corneal tissue.

Comparison of femtosecond laser-assisted deep anterior lamellar keratoplasty and penetrating keratoplasty for keratoconus.

BACKGROUND: To compare outcomes of femtosecond laser-assisted deep anterior lamellar keratoplasty (FSL-DALK) and penetrating keratoplasty (FSL-PK) for the treatment of keratoconus. METHODS: Twenty eight eyes underwent FSL-DALK (consisted of 12 eyes in the FSL-DALKa subgroup without baring the Descemet's membrane and 16 eyes in the FSL-DALKb subgroup baring the Descemet's membrane using big-bubble technique) were compared with 12 eyes that underwent FSL-PK for keratoconus. These patients underwent an ophthalmic examination preoperatively and 3, 6, 9, and 12 months postoperatively. RESULTS: The postoperative BCVA in the FSL-PK group, and the FSL-DALKb subgroup were significantly better than that in the FSL-DALKa subgroup (P < 0.05), whereas no differences were found between the FSL-DALKb subgroup and the FSL-PK group (P > 0.05). There were no significant differences in the mean spherical equivalent (SE) and astigmatism between the FSL-DALK and the FSL-PK groups, nor between the subgroups of FSL-DALK during the follow-up period (P > 0.05). At the last follow-up, the mean endothelial cell loss in the FSL-DALK group (9.12 %) was significantly less than that in the FSL-PK group (20.79 %) (P < 0.001), while there was no difference between the FSL-DALKa (9.15 %) and the FSL-DALKb (9.10 %) subgroups (P = 0.15). The FSL-DALK group seemed to have fewer graft rejections (1/28 cases) than the FSL-PK group (2/12 cases), although Kaplan-Meier curve showed no significant difference between the two groups (P = 0.144). CONCLUSIONS: In this retrospective study, the results suggested that FSL-DALKb gives better visual outcome, and FSL-DALKb is a better option for keratoconus whose endothelium is not compromised. However, larger and prospective studies are further required.

[Treatment of large corneal perforations with acellular multilayer of corneal stromal lenticules harvested from femtosecond laser lenticule extraction].

OBJECTIVE: To describe a novel surgical technique for the treatment of large corneal perforations by using acellular multilayer of corneal stromal lenticules. METHODS: Prospective study. The acellular tissue used for the repair was harvested from myopic patients during the femtosecond laser (FS) refractive surgery. Informed consent, blood test and donor eligibility were obtained in each case. Three or four layers of lenticules were stacked up and stored at -80°C in pure sterile glycerin. The diameter is 6.0 to 6.5 mm and central thickness was 300 to 400 µm. If the diameter of the corneal ulcer perforation was larger than 3 mm and corneal grafts were not available, we used this kind of patches to seal the perforations. It was a retrospective case series study. Five cases of corneal ulcer perforation were enrolled in this study. One was neuropathic keratitis, one was atopic keratoconjunctivitis, and the other three were fungal keratitis. Acellular multilayer of stromal lenticules were used in these cases for emergent therapy. RESULTS: The sealing of the perforation and the re-establishment of the anterior chamber were achieved successfully in all the cases. For the pericentral perforations, visual recovery was achieved. And efficient palliative management was done for the central perforations. CONCLUSIONS: The reported technique seems to represent a good alternative emergency procedure for the management of large corneal perforations. It is a very useful method for Chinese hospitals where the shortage of cornea donors is a very serious problem and the amount of FS surgeries are increasing.

Tolerogenic dendritic cells suppress murine corneal allograft rejection by modulating CD28/CTLA-4 expression on regulatory T cells.

Anterior chamber-associated immune deviation (ACAID) is initiated when dendritic cells (DCs) capture intraocular antigen and induce regulatory T cells (Tregs) in the spleen. We investigated whether DCs could be used as an immunotherapy to prevent murine corneal allograft rejection by inducing Tregs. Bone marrow-derived DCs (BMDCs) were differentiated with transforming growth factor-ß2 (TGF-ß2) in the presence of donor-derived allopeptide in vitro (TGFß2-DCs), and adoptively transferred to BALB/c mice. Three days later a corneal allograft transplant was carried out. Graft rejection, as well as the number and the phenotype of splenic Tregs, were determined after transplant. CD86, CD80, CD40 were present, and MHC class II expression were significantly reduced on TGFß2-DCs compared to BMDCs not exposed to TGF-ß2. TGFß2-DCs increased the number of splenic Tregs (CD4(+)CD25(+)) in recipient mice prior to transplant by modulating CD28/CTLA-4 expression. These induced Tregs suppressed proliferation of CD4(+)CD25(-) T cells ex vivo. TGFß2-DCs delayed corneal allograft rejection and TGFß2-DC recipient mice had significantly more splenic Tregs expressing Foxp3 and CTLA-4, but fewer CD28+ Tregs. Expression of GITR, CD69, and CD45RB were similar in TGFß2-DC and control mice. Therefore, the phenotype of TGFß2-DCs suggests they are tolerogenic DCs (tolDCs). In vivo, these cells increased the number and function of Tregs by modulating CD28/CTLA-4 expression. The suppressor Tregs induced by TGFß2-DCs may be involved in the induction of ACAID, which helps to suppress corneal allograft rejection. Our results provide proof of principle for the use of tolDCs as immunotherapy during transplant.

[The clinical results of femtosecond laser-assisted deep anterior lamellar keratoplasty in patients with keratoconus].

OBJECTIVE: To evaluate the clinical results and safety of deep anterior lamellar keratoplasty (DALK) in patients with keratoconus assisted by a femtosecond laser. METHODS: Six eyes of 5 patients with keratoconus underwent DALK procedures by using a femtosecond laser. The mean thinnest corneal thickness, evaluated with ultrasound and measurement of visual acuity by using the standard logarithm visual chart. A femtosecond laser was used to perform corneal cuts on both donor and recipient corneas. The data were expressed as mean ± SD. Mean follow-up was (8.9 ± 2.3) month (range, 5-12 months) . RESULTS: Corneal pachymetry was (385 ± 48) µm (range, 380-460 µm) . Mean preoperative uncorrected visual acuity was 0.06 ± 0.06 (range,0.01-0.15) and mean preoperative best spectacle-corrected visual acuity was 0.41 ± 0.35 (range,0.12-1.00) . The donor corneal lamella diameters were 0.20 mm larger and thicker than the recipient to restore a physiologic corneal thickness and shape. Mean donor diameter was (7.8 ± 0.2) mm (range, 7.3-8.0 mm) and mean thickness was (372 ± 40) µm (range, 350-400 µm) .Early postoperative evaluation showed a clear graft in all cases. Mean corneal thickness was (459 ± 36) µm (range, 389-488 µm) . At the last postoperative examination mean uncorrected visual acuity was 0.32 ± 0.19 (range, 0.12-0.60) , and the mean best corrected visual acuity was 0.58 ± 0.29 (range,0.20-1.00) . The UCVA and BCVA improved significantly after surgery (t = -4.433, -3.348, P < 0.05). CONCLUSIONS: Our early results indicate that femtosecond laser-assisted deep anterior lamellar keratoplasty shows promise as a safe and effective surgical choice in the treatment of keratoconus.

Mesenchymal Stem Cells Regulate Microglial Polarization via Inhibition of the HMGB1/TLR4 Signaling Pathway in Diabetic Retinopathy.

Diabetic retinopathy (DR) is recognized as the most prevalent retinal degenerative disorder. Inflammatory response usually precedes microvascular alteration and is the primary factor of diabetic retinopathy. Activated microglia express many pro-inflammatory cytokines that exacerbate retina inflammation and disruption. In the present study, we found that MSCs alleviated blood-retina barrier (BRB) breakdown in diabetic rats, as evidenced by reduced retinal edema, decreased vascular leakage, and increased occludin expression. The MSC-treated retinal microglia exhibited reduced expression of M1-phenotype markers in the diabetic rats, including inducible nitric oxide synthase (iNOS), CD16, and pro-inflammatory cytokines. On the other hand, MSCs increased the expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206, and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is activated in DR and inhibited after MSC treatment. Consistent with in vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro. Overexpression of HMGB1 in microglia reversed the effects of MSC treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs' regulatory effects on microglia polarization. Collectively, MSCs exert beneficial effects on DR by polarizing microglia from M1 toward M2 phenotype via inhibiting the HMGB1/TLR4 signaling pathway.

Two polymorphisms (rs699947, rs2010963) in the VEGFA gene and diabetic retinopathy: an updated meta-analysis.

BACKGROUND: The vascular endothelial growth factor (VEGFA) gene has been suggested to play an important role in the pathogenesis of diabetic retinopathy (DR). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between VEGFA polymorphisms and DR risk. METHODS: Published literature from PubMed, EMBASE, Web of Science and Google Scholar were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. RESULTS: A total of eight studies (1204 cases and 1198 controls) for rs699947 polymorphism and ten studies (1666 cases and 1782 controls) for rs2010963 polymorphism were included in the meta-analysis. The results suggested that rs699947 polymorphism was marginally associated with DR under a homogeneous co-dominant model (AA vs. CC: OR = 1.69, 95% CI = 1.03-2.77, p = 0.040) and a dominant model (AA + AC vs. CC: OR = 1.38, 95% CI = 1.01-1.90, p = 0.040), whereas the association between rs2010963 polymorphism and DR was not significant under all genetic models (all p > 0.05). In the subgroup analysis, the effect size for rs699947 polymorphism was only marginally significant among European populations under a dominant model (OR = 1.47, 95% CI = 1.07-2.02, p = 0.018), but not among East Asians. After exclusion of outliers which were the source of between-study heterogeneity, there was significant association between rs699947 polymorphism and DR under a homogeneous co-dominant model (OR = 1.64, 95% CI = 1.18-2.28, p = 0.003), even after multiple comparison correction. CONCLUSIONS: Our meta-analysis confirmed the significant association between rs699947 polymorphism and DR after exclusion of outliers, and rs2010963 polymorphism might be not associated with DR.

METTL3-mediated m6A RNA modification promotes corneal neovascularization by upregulating the canonical Wnt pathway during HSV-1 infection.

BACKGROUND: Corneal neovascularization (CNV) is a symptom of herpes simplex keratitis (HSK), which can result in blindness. The corneal angiogenesis brought on by herpes simplex virus type 1 (HSV-1) is strongly affected by vascular endothelial growth factor A (VEGFA). The N6-methyladenosine (m6A) modification catalyzed by methyltransferase-like 3 (METTL3) is a crucial epigenetic regulatory process for angiogenic properties. However, the roles of METTL3 and m6A in HSK-induced CNV remain unknown. Here, we investigated these roles in vitro and in vivo. METHODS: A PCR array in HSV-1-infected human umbilical vein endothelial cells (HUVECs) was used to screen for METTL3 among the epitranscriptomic genes. Tube formation and scratch assays were conducted to investigate cell migration capacity. The global mRNA m6A abundance was evaluated using a dot blot assay. Gene expression was assessed by RT-qPCR, western blotting, and fluorescence immunostaining. In addition, bioinformatic analysis was conducted to identify the downstream molecules of METTL3 in HUVECs. METTL3 knockdown and STM2457 treatment clarified the specific underlying molecular mechanisms affecting HSV-1-induced angiogenesis in vitro. An acute HSK mouse model was established to examine the effects of METTL3 knockdown or inhibition using STM2457 on pathological angiogenic development in vivo. RESULTS: METTL3 was highly upregulated in HSV-1-infected HUVECs and led to increased m6A levels. METTL3 knockdown or inhibition by STM2457 further reduced m6A levels and VEGFA expression and impaired migration and tube formation capacity in HUVECs after HSV-1 infection. Mechanistically, METTL3 regulated LRP6 expression through post-transcriptional mRNA modification in an m6A-dependent manner, increasing its stability, upregulating VEGFA expression, and promoting angiogenesis in HSV-1-infected HUVECs. Furthermore, METTL3 knockdown or inhibition by STM2457 reduced CNV in vivo. CONCLUSION: Our findings revealed that METTL3 promotes pathological angiogenesis through canonical Wnt and VEGF signaling in vitro and in vivo, providing potential pharmacological targets for preventing the progression of CNV in HSK.

Pooled-analysis of the associations between three polymorphisms in the VEGF gene and age-related macular degeneration.

The vascular endothelial growth factor (VEGF) gene has been suggested to play an important role in the pathogenesis of age-related macular degeneration (AMD). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between VEGF polymorphisms and AMD risk across different populations. Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Five studies (1,280 cases and 715 controls) for rs833061 polymorphism, five studies (1,033 cases and 807 controls) for rs1413711 polymorphism, and four studies (1,217 cases and 4,079 controls) for rs2010963 polymorphism were identified. No statistically significant association was found for rs833061, rs1413711 and rs2010963 polymorphisms, although there were significant associations for rs833061 polymorphism under a homogeneous co-dominant model (CC vs. TT: OR = 1.59, 95%CI 1.14-2.23) and for rs1413711 polymorphism under a recessive model (TT vs. CT + CC: OR = 1.50, 95%CI 1.08-2.08), the results were not robust by sensitivity analysis. However, there was a significant association for rs833061 among European and East Asian populations, and for rs1413711 among Europeans. The present meta-analyses indicated that there were no significantly associations between VEGF polymorphisms (rs833061, rs1413711, rs2010963) and the risk of AMD, although the association was different for each polymorphism among different populations.

Preliminary Assessment of Intramuscular Depot of Lipid-Based Decoquinate Formulation for Long-Term Chemoprophylaxis of Malaria.

Sustained-release formulations of decoquinate were evaluated for the long-term prophylaxis of malaria. In the initial experiment, mice were protected from liver-stage Plasmodium infection by intramuscular administration of a lipids-based formulation at a dose of decoquinate 200 mg/kg. The mice that were inoculated with Plasmodium berghei sporozoites 34 days after the administration of a one-time drug dose were continuously monitored for 60 days and shown to be free of Plasmodium parasites. The optimized formulation for the sustained release of decoquinate was prepared by hot melt extrusion, constructed by lipids including cholesterol and mono or diglycerides, and had a drug load of 20 to 40% and particle size of 30 to 50 µm. Decoquinate of the lipids-based formulation was slowly released in vitro at a constant rate for the duration of two months, and was examined and continuously exposed at a therapeutic level in the blood for as long as 4 to 6 months. Further evaluation showed that the lipids-based formulation at doses of decoquinate 100 to 150 mg/kg could protect mice from Plasmodium infection for a period of 120 days. It is the first time that cholesterol has been used for a controlled drug delivery system of decoquinate. The results may provide useful information, not only for preparing a formulation of long-acting decoquinate but also in general for developing a controlled drug release system. The one-time administration of pharmaceutical agents in such a slow-release system may serve patients with no concerns about compliance.

Tin Oxide (SnO2) Nanoparticles: Facile Fabrication, Characterization, and Application in UV Photodetectors.

Tin oxide (SnO2) nanomaterials are of great interest in many fields such as catalytic, electrochemical, and biomedical applications, due to their low cost, suitable stability characteristics, high photosensitivity, etc. In this contribution, SnO2 NPs were facilely fabricated by calcination of tin (II) oxalate in air, followed by a liquid-phase exfoliation (LPE) method. Size-selected SnO2 NPs were easily obtained using a liquid cascade centrifugation (LCC) technique. The as-obtained SnO2 NPs displayed strong absorption in the UV region (~300 nm) and exhibited narrower absorption characteristics with a decrease in NP size. The as-fabricated SnO2 NPs were, for the first time, directly deposited onto a poly(ethylene terephthalate) (PET) film with a regular Ag lattice to fabricate a flexible working electrode for a photoelectrochemical (PEC)-type photodetector. The results demonstrated that the SnO2-NP-based electrode showed the strongest photoresponse signal in an alkaline electrolyte compared with those in neutral and acidic electrolytes. The maximum photocurrent density reached 14.0 µA cm-2, significantly outperforming black phosphorus nanosheets and black phosphorus analogue nanomaterials such as tin (II) sulfide nanosheets and tellurene. The as-fabricated SnO2 NPs with relatively larger size had better self-powered photoresponse performance. In addition, the as-fabricated SnO2-NP-based PEC photodetector exhibited strong cycling stability for on/off switching behavior under ambient conditions. It is anticipated that SnO2 nanostructures, as building blocks, can offer diverse availabilities for high-performance self-powered optoelectronic devices to realize a carbon-neutral or carbon-free environment.

Nectin-1 and Non-muscle Myosin Heavy Chain-IIB: Major Mediators of Herpes Simplex Virus-1 Entry Into Corneal Nerves.

Herpes Simplex Virus 1 (HSV-1) invades corneal nerves upon its infection of the cornea and then establishes latency in the trigeminal ganglion (TG). The latent virus in TG is often reactivated and travels back to the cornea, causing recurrent herpes simplex keratitis (HSK). The entry of HSV-1 into the corneal nerve is considered the initial step of infection resulting in HSV-1 latency and HSK recurrence. Several gD and gB receptors have been identified, including nectin-1, herpes virus entry medium (HVEM) and 3-O-sulfated heparan sulfate (3-OS-HS) as gD receptors, and non-muscle myosin heavy chain IIA (NMHC-IIA), NMHC-IIB and myelin-associated glycoprotein (MAG) as gB receptors. However, which receptors contribute to the entry of HSV-1 into corneal nerves are yet to be determined. This study observed that receptors nectin-1, HVEM, 3-OS-HS, NMHC-IIA, and NMHC-IIB, not MAG, were expressed in healthy corneal nerves. Further, we cultured TG neurons extracted from mice in vitro to screen for functional gD/gB receptors. Both in vitro siRNA knockdown and in vivo antibody blocking of either nectin-1 or NMHC-IIB reduced the entry and the replication of HSV-1 as shown by qPCR analysis and immunofluorescence measure, respectively. Also, we observed that the re-localization and the upregulation expression of NMHC-IIB after HSV-1 exposure were inhibited when gD receptor nectin-1 was knocked down. These data suggest that nectin-1 was the main gD receptor and NMHC-IIB was the main gB receptor in mediating HSV-1 entry and hold promise as therapeutic targets for resolving HSV-1 latency and HSK recurrence.