Downregulation of Long Noncoding RNA MIAT in the Retina of Diabetic Rats with Tail-vein Injection of Human Umbilical-cord Mesenchymal Stem Cells.

Diabetic retinopathy (DR) is the common and important cause for visual impairment and blindness in working-aged people. Microangiopathy and inflammatory reactions are the key components of DR. Recently, long non-coding RNA myocardial infarction-associated transcript (MIAT) has emerged as a vital player in regulation for inflammatory processes and microvascular dysfunction. Additionally, cell-based therapy provides a potential option for the treatment of DR. The anti-inflammatory effects and repair therapy of mesenchymal stem cells (MSCs) have been paid more attention. This study investigated the effects of human umbilical-cord mesenchymal stem cells (HUMSCs) injection on diabetic rat model. The results show that the level of MIAT is significantly decreased in the diabetic retina after the injection of HUMSCs. Moreover, HUMSCs can significantly decrease the expression of IL-1ß and IL-6 mRNA; alleviate microvascular permeability, and upregulate Occludin expression. Studies have shown that MIAT knockdown could alleviate diabetes-induced inflammation responses and vascular leakage. Furthermore, our findings also showed that the expression of MIAT was positively correlated with the expression of IL-1ß and IL-6. These results suggest that MIAT might play important regulatory roles in alleviating inflammatory reactions and microangiopathy inducing by DR after transplantation of HUMSCs.

Structural and functional assessment after intravitreal injection of ranibizumab in diabetic macular edema.

PURPOSE: To evaluate structure and function improvement in central retina by optical coherence tomography (OCT) and multifocal electroretinography (mf-ERG) in diabetic macular edema (DME) patients after intravitreal injection of ranibizumab (IVR) treatment. METHODS: Twenty-seven eyes in 27 patients with DME received three consecutive monthly injections of IVR (0.05 ml, 10 mg/ml) and as needed thereafter. The clinical parameters of best-corrected visual acuity (BCVA), central foveal thickness (CFT) and mf-ERG were monitored for 6 months before and after IVR. The findings at baseline, 1, 3 and 6 months were analyzed. Correlation and regression analyses were performed on BCVA, CFT, mf-ERG amplitude and implicit time of the N1 and P1 waves. RESULTS: IVR significantly improved visual acuity from the beginning of the treatment (P < 0.05). There were significant decreases in the CFT compared with the baseline after IVR (P < 0.05). The mean amplitude of P1 and N1 in the central ring at all examinations increased significantly compared with the baseline (P < 0.05). The mean P1 and N1 implicit times in the central ring were shortened, but not significantly (P > 0.05). There were significant correlations of BCVA with CFT, P1 and N1 amplitudes in the central retina (P < 0.05). CONCLUSION: In addition to the improvement in BCVA and the reduction in CFT, IVR improved macular retinal function, as assessed by mf-ERG, in diabetic eyes. The combination of OCT and mf-ERG for macular evaluation may better assess DME.

Effect of plasma-derived extracellular vesicles on angiogenesis and the ensuing proliferative diabetic retinopathy through a miR-30b-dependent mechanism.

BACKGROUND/PURPOSE: Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication, characterized by pathological angiogenesis. This study sets out to investigate the potential molecular mechanism in the angiogenesis during PDR. METHODS: The expression of microRNA-30b (miR-30b) was quantified in a streptozotocin (STZ)-induced mouse model of PDR. The binding affinity between SIRT1 and miR-30b was then identified and validated. After transduction with In-miR-30b or combined with sh-SIRT1, high-glucose (HG)-induced retinal microvascular endothelial cells (RMECs) were co-cultured with extracellular vesicles (EVs) derived from the plasma of PDR mice (plasma-EVs). The proliferation and angiogenesis of RMECs were then detected in vitro. RESULTS: miR-30b expression was upregulated in the retinal tissue of PDR mice. SIRT1 was a target gene of miR-30b and under the negative regulation by miR-30b in RMECs. In contrast, inhibition of miR-30b resulted in elevated SIRT1 expression, thus alleviating the angiogenesis of RMECs. miR-30b was enriched in the plasma-EVs and could be delivered to RMECs, in which miR-30b exerted pro-angiogenic effects. Furthermore, inhibition of miR-30b arrested the progression of PDR in mice by promoting the expression of SIRT1. CONCLUSION: Collectively, the present study pinpointed the involvement of miR-30b delivered by plasma-EVs in PDR angiogenesis, thus laying the basis for the development of novel therapeutic targets for the treatment of PDR.

Silenced SNHG1 Inhibited Epithelial-Mesenchymal Transition and Inflammatory Response of ARPE-19 Cells Induced by High Glucose.

PURPOSE: The lncRNA small nucleolar RNA host gene 1 (SNHG1) is a cerebral infarction-associated gene, its biological role and mechanism in diabetic retinopathy remain to be illuminated. The present study was designed to investigate the role of SNHG1 in high glucose induced human retinal pigment epithelial cells (ARPE-19). METHODS: ARPE-19 cells were cultured and exposed to 60 mM high glucose for 48h, and 5.5mM glucose-exposed ARPE-19 cells were used as the control. The levels of the epithelial-mesenchymal transition (EMT) markers E-cadherin, ZO-1, vimentin and α-SMA were measured, and the Cell inflammatory response was evaluated by detecting IL-6 and IL-1ß levels. Then, cell migration, proliferation and apoptosis were detected. The expression of the lncRNA SNHG1 in ARPE-19 cells was detected by quantitative real-time PCR. SNHG1 was knocked down by small interfering RNA (siRNA) transfection. The effects of SNHG1 inhibition on inflammation, EMT, migration, proliferation and apoptosis were observed. RESULTS: The results showed that the expression of SNHG1 was significantly increased in ARPE-19 cells exposed to high glucose. Silencing SNHG1 reduced the expression of vimentin, α-SMA, and the expression of inflammatory chemokines IL-6 and IL-1ß, inhibited migration and proliferation, elevated the expression of E-cadherin and ZO-1, and promoted apoptosis in ARPE-19 cells. CONCLUSION: The lncRNA SNHG1 is involved in hyperglycemia-induced EMT and the inflammatory response of ARPE-19 cells and provides a new understanding of the pathogenesis of DR.

Clinical effects of three types of silicone intubations in repairing lacerations of canaliculus.

OBJECTIVE: To evaluate the clinical effects of one-passage, double-passage and circular canalicular intubations in repairing lacerations of canaliculus. METHODS: A total of 109 eyes in 109 cases of canalicular laceration were repaired with three types of silicone intubations, among which 23 with one-passage canalicular intubation, 51 with double-passage canalicular intubation, and 35 with circular canalicular intubation. The average follow-up period was 12-15 months. RESULTS: The wound/junction of the lacrimal canaliculi was ruptured in 5 cases (9.80%) of the double-passage group, 3 cases (8.57%) of the circular group, and 8 cases (34.78%) of the one-passage group. The rupture incidence of the one-passage group was significantly higher than that of the other two groups (X(2) equal to 9.416, P less than 0.01). During the intubation, canaliculitis was observed in 12 cases (23.53%) of the double-passage group, while only 3 cases (8.57%) in the circular group and 8 cases (34.78%) in the one-passage group. The circular group had significantly lower incidence of canaliculitis than the other two groups (X(2) equal to 6.095, P less than 0.05). After extubation 6 months after laceration repair, the lacrimal passage remained patent with canalicular irrigation in 46 cases (90.20%) in the double-passage group, 30 cases (85.71%) in the circular group and 15 cases (65.22%) in the one-passage group. Six months after surgery, the canalicular patency in the one-passage group was significantly lower than that of the other two groups (X(2) equal to 7.390, P less than 0.05). CONCLUSIONS: Circular canalicular intubation is more stable and has less surgical complications than the double-passage and one-passage canalicular intubations. It is also more effective clinically 12-15 months after laceration surgery.

Corrigendum to "Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry".

[This corrects the article DOI: 10.1155/2018/3567647.].

Development of Corneal Astigmatism (CA) according to Axial Length/Corneal Radius (AL/CR) Ratio in a One-Year Follow-Up of Children in Beijing, China.

PURPOSE: The correlations between the axial length-to-corneal radius (AL/CR) ratio and corneal astigmatism (CA) were studied by prospectively analyzing and comparing survey data from school children in the Beijing urban area from 2014 to 2015. METHODS: In this longitudinal study, a total of 2,970 students were enrolled in 2014, and 2,179 students were enrolled in 2015. The students were in grades 1 and 4 of primary schools located in the Yangfangdian district of Beijing. The students were examined using the standard logarithmic visual acuity chart for uncorrected visual acuity (UCVA) and IOLMaster for ocular components. RESULTS: From 2014 to 2015, the students from grades 1 and 4 had significantly worse UCVA results, longer axial lengths (AL), and greater AL/CRs (p < 0.001). The boys had a longer AL and corneal radius (CR) than the girls (p < 0.001). A significantly higher rate of increased CA was observed for the students with increased AL/CR than for those with decreased or unchanged ratios (AL/CR for grade 1, X2 = 12.304, p=0.001; for grade 4, X2 = 29.044, p < 0.001). In addition, with increased AL/CR over one year, the CA value of the students in grades 1 and 4 became significantly larger (grade 1, p=0.001; grade 4, p < 0.001); moreover, the UCVA became worse (p < 0.001). CONCLUSIONS: We found that UCVA and AL growth were affected by aging. An increase in the AL/CR ratio is a risk factor for the progression of corneal astigmatism for school children.

Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry.

Dictamnine (4-methoxyfuro[2,3-b]quinolone, DIC), a common furoquinoline alkaloid in the family of Rutaceae, showed diverse biological activities. To investigate the in vivo metabolic pathways of DIC, metabolism of DIC in mice was studied using a high-performance liquid chromatography coupled to electrospray ionization of hybrid linear trap quadrupole orbitrap (HPLC-LTQ-Orbitrap) mass spectrometer. Nine metabolites were identified in the DIC-treated mouse urine, plasma, and fecal samples, of which two were identified as new metabolites. The major metabolic pathways of DIC in animal and human liver microsomes were confirmed in the present study, including o-demethylation, monohydroxylation, N-oxidation, and 2,3-olefinic epoxidation pathways. For the first time, a mono-acetylcysteine conjugate of DIC (M9) was detected from DIC-treated mouse urine and plasma samples, and 4-methoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (M10) and 2-(2,8-dihydroxy-4-methoxyquinolin-3-yl)acetaldehyde (M11) were identified as new metabolites of DIC; furthermore, using an in vitro human fecal incubation model, furo[2,3-b]quinolin-4-ol (M1) was verified to be a microbial demethylated metabolite of DIC. Collectively, the present study provided new information on the in vivo metabolic fate of DIC.

Neuron-derived netrin-1 and netrin-4 proteins are additional effective targets in diabetic retinopathy beyond VEGF.

Vascular endothelial growth factor (VEGF) is the typical representative factor of diabetic retinopathy (DR) and is considered to be a key inducer of retinal vascular permeability in DR. Anti-VEGF has been widely used in clinical treatment but every patient is effective, therefore, it is necessary to find other effective factors that participate in the pathology of DR. We provide evidence from both human and animal experiments for the considerable roles of classical neuronal guidance factors, netrin-1 and netrin-4, in indicating and amending the pathology of DR. We reveal that levels of both netrin-1 and netrin-4 are reduced while VEGF increases in DR patients and animal models. We demonstrate through different experimental methods that augmenting netrin-1 and netrin-4 can alleviate vasculopathy and neuropathy which appear in DR. Our findings offer additional effect targets besides VEGF for DR and suggest we should increase the focus on neurovascular crosstalk as DR is a neurovascular disease.

Clinical analysis of hydroxyapatite orbital implantation after ocular trauma in 211 cases.

OBJECTIVE: To evaluate the therapeutic effects and complications of hydroxyapatite (HA) orbital implantation on patients after trauma-related surgeries. METHODS: Retrospective analysis was made from 211 cases (211 eyes) who underwent HA orbital implant placement after trauma-related enucleation or evisceration, including 68 cases of evisceration and primary HA implant placement, 77 cases of enucleation and HA implant placement wrapped with multi-windowed sclera, 66 cases of enucleation and HA implant placement free of wrapping. All the cases were followed up for 1-5 years to observe the therapeutic effects and major complications. RESULTS: Five of 211 cases had wound dehiscence. Ten cases had HA implants exposure, including 1 case suffering severe orbital infection and requiring HA implant removal. The implants exposure incidences by the three surgical methods were from 1.30% to 10.06% and averaged 4.74%. Significant difference was found in late exposure incidence and total incidence from the three methods (chi(2)=13.372, P < 0.01 and chi(2)=7.540, P < 0.05). Two cases had shrinkage of the lower fornix. Enophthalmos occurred in 1 case treated by method 1 and was corrected by implanting porous polyethylene (Medpor) plate into the bottom of orbit. In 210 cases, the artificial eye moved well and the cosmetic results were satisfactory. CONCLUSIONS: Different surgical methods have their own merit and disadvantage. Enucleation and placement of HA implant wrapped with multi-windowed sclera has corroborated fewer complications than others.

Treatment for amblyopia after surgery for cataract and vitreoretina in pediatric ocular trauma.

PURPOSE: We investigated the value of occlusion therapy assisted by wearing spectacles or implanting an intraocular lens following surgeries for cataract and vitreoretina in pediatric pa-tients. METHODS: Fifty-one children with ocular trauma, aged from 3 to 12 years, were enrolled in this study, including 39 cases of open global injuries and 12 ocular blunt injuries. The patients underwent a series of surgeries, including suture of the cornea or sclera wound, cataract extraction, vitrectomy, and repair of retinal detachment in some cases. Occlusion therapy was prescribed for 29 eyes wearing spectacles and 22 eyes with implanted intraocular lenses (IOLs) for 6 to 12 months. All the children were followed up for 12 to 60 months (mean 41.5 months) after the final operations. RESULTS: Best corrected visual acuity was improved in 32 eyes (62.7%) and not improved in 19 eyes (37.3%), including 6 eyes with a leucoma involving the central cornea, 5 eyes with a retina scar involving the macula, and 2 eyes with unsatisfactory overall patching time. Occlusion therapy assisted by wearing spectacles (65.5%) and implanting IOLs (59.1%) showed similar improvements in the visual acuity of the injured eyes. CONCLUSION: Occlusion therapy, combined with wearing spectacles and implanting IOLs, is valuable in treating deprivation amblyopia due to ocular trauma and series surgeries in pediatric patients. Spectacles may be dependable during occlusion therapy in the early post-surgery stage.

Visual outcome following intraocular foreign bodies: a retrospective review of 5-year clinical experience.

PURPOSE: To determine the main prognostic factors related to final visual acuity (VA) after intraocular ocular foreign body (IOFB) extraction. METHODS: We performed a retrospective chart review of 80 patients (84 eyes) who underwent surgical removal of IOFBs and repair of associated ocular trauma. Data on age, gender, presenting clinical features, characteristics of IOFB, complications, interval between time of injury and IOFB removal, and final VA were recorded and analyzed. RESULTS: Male adults were the major population affected by IOFBs. Improved vision outcome was obtained after the removal of IOFBs and surgical repair of the eyes (p=0.011). Factors showing statistical association with final VA included initial VA (p=0.000), size of IOFB (p=0.010), IOFB location inside the eye (p=0.000), and preoperative retinal detachment (p=0.011). Factors showing no statistical association with final VA included nature of IOFB (p=0.445), entrance wound location, other IOFB-related complications (such as cataract, vitreous hemorrhage, secondary glaucoma, hyphema, endophthalmitis, siderosis, and atrophia bulbi), and interval between injury and IOFB removal. CONCLUSIONS: Prognostic factors for poor final VA related to IOFBs included poor initial VA, large IOFB size, posterior segment location, and preoperative retinal detachment.