Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity: An Assessment of Panretinal Leakage Index, Ischemic Index and Microaneurysm Count.

PURPOSE: To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count. DESIGN: Retrospective image analysis study. METHODS: Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history. MAIN OUTCOME MEASURES: Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count. RESULTS: Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P<2×10-16], panretinal ischemic index [mild NPDR (mean = 0.95%, moderate NPDR (mean = 1.37%), severe NPDR (mean = 2.80%), and PDR (mean = 9.53%); P<2×10-16], and panretinal microaneurysm count [mild NPDR (mean = 36), moderate NPDR (mean = 129), severe NPDR (mean = 203), and PDR (mean = 254); P<5×10-7] were strongly associated with DR severity. Multivariate analysis demonstrated that ischemic index and leakage index were the parameters associated most strongly with level of DR severity. CONCLUSIONS: Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm count are associated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.

Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China.

The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 µg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (P<0·05). Moreover, the proportion of vitamin A deficiency, marginal vitamin A deficiency and Fe deficiency among children in group 3 were markedly lower compared with children in groups 1 and 2 (P<0·05). Albendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status.

An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region.

OBJECTIVE: We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status. DESIGN: Descriptive review conducted on English publications reporting breast-milk DHA and AA levels. SETTING: We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included. SUBJECTS: Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals. RESULTS: Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, P<0·05). Data from the Asian region showed the highest DHA concentration but much lower AA concentration in breast milk compared with all other regions, independent of accessibility to marine foods. Comparison was made among Canada, Poland and Japan - three typical countries (each with sample size of more than 100 women) from different regions but all with high income and similar accessibility to fish/marine foods. CONCLUSIONS: The current review provides an update on worldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations.

Suppression of Chlorantraniliprole Sorption on Biochar in Soil-Biochar Systems.

The sorption behavior of chlorantraniliprole (CAP) by biochar and effect of soil extracts on sorptivity in soil-biochar systems were examined. The results showed that biochar amendment could enhance the sorption of CAP in soils. The values of K F increased significantly when the soils were amended with 0.5 % BC850, which were from 1.54 to 196.5. The indigenous sorptivity of biochar was suppressed after it was applied to the soils. The degree of biochar sorptivity attenuation in different soil-biochar systems varied with the properties of soil water soluble matters. Sorption of CAP by biochar from the five soil extracts was found to be lower than that from a CaCl2 solution. The calculated K d values at C w of 0.01 mg kg(-1) for biochar sorption of CAP from CaCl2 solution were 21.4-26.6 times of that from soil extracts. Aging of biochar in soil extract reduced CAP sorption by up to 85 %.

Unilateral progressive keratoconus associated with ipsilateral craniofacial fibrous dysplasia treated with corneal cross-linking.

Purpose: The purpose of this study is to describe a case of unilateral keratoconus associated with ipsilateral craniofacial fibrous dysplasia and its subsequent management with corneal collagen cross-linking. Observations: This is an interventional case report of a 16-year-old male with a history of polyostotic fibrous dysplasia of the left frontal bone and orbital roof status post partial resection six years prior who presented to the pediatric ophthalmology clinic with progressively blurry vision in the left eye. Refraction in this eye revealed an increase in cylinder by > 3D from his last refraction two years prior. Pentacam corneal tomography confirmed the diagnosis of keratoconus in the left eye. The patient underwent corneal collagen cross-linking in the affected eye. Postoperatively, he experienced marked improvement in corrected visual acuity with scleral contact lenses and maintained stable astigmatism and keratometry values on Pentacam corneal tomography at his most recent visit 12 months postoperatively. Conclusions: While it is otherwise felt to be a bilateral disease, unilateral keratoconus may present in the context of ipsilateral orbital pathology. Corneal collagen cross-linking may be used to successfully prevent keratoconus progression in the setting of stable orbital pathology.

Femtosecond laser lenticule transplantation in rabbit cornea: experimental study.

PURPOSE: To evaluate the feasibility of femtosecond laser-induced lenticule transplantation in the rabbit cornea and to observe the relative histologic characteristics of corneal tissue and nerve repair after transplantation. METHODS: Eight healthy, purebred, New Zealand white rabbits underwent femtosecond laser small-incision lenticule extraction (SMILE) surgery in the right eye. Lenticules were inserted into a femtosecond laser-created corneal stromal pocket in the left eye, which was defined as femtosecond laser corneal lenticule transplantation. Postoperative observation and examination were completed to evaluate the surgery. RESULTS: In the early postoperative period, inflammation of the cornea was noted, tissue around the lenticule was edematous, and cells were activated. Tissue edema remained at postoperative day 10. By 1 month, edema had resolved, activated cells gradually became quiescent, and nerve fiber regeneration was observed. By 3 months, the lenticule integrated into the recipient cornea, extracellular matrix gradually cleared, and thicker nerve fibers were noted. By 6 months postoperative, morphology and distribution of the corneal stromal fibers were close to normal, and the number of nerve fibers was reduced. CONCLUSIONS: Femtosecond laser corneal lenticule transplantation in rabbits is feasible, as the lenticule was shown to thrive and integrate with the recipient stroma. Nerve regeneration begins after 1 month.

Effect of preoperative retinal sensitivity and fixation on long-term prognosis for idiopathic macular holes.

BACKGROUND: To study the roles of preoperative retinal sensitivity and fixation exams in predicting the long-term prognosis of idiopathic macular hole (IMH) patients after successful vitrectomy. METHODS: A total of 39 IMH patients (39 eyes) were included in this prospective cohort case series study. Twenty-three gauge pars plana vitrectomy was performed on each patient. Results of best-corrected visual acuity (BCVA), macular hole diameter, MP - 1 microperimetry (MP - 1) tests, and continuity of the photoreceptor inner and outer segment (IS/OS) junction were recorded for analysis. RESULTS: Postoperative BCVA at 12 months was significantly correlated with macular hole diameters (p < 0.05), preoperative BCVA (p = 0.020), mean retinal sensitivity (p < 0.001), and fixation location percentage (p < 0.001). However, merely preoperative mean retinal sensitivity (r = 0.5448, p < 0.001) and fixation location percentage (r = 0.5624, p < 0.001) were suggested to be quantitatively predictive for the visual prognosis by multiple stepwise linear regression analysis. Moreover, patients that had smaller hole sizes (p < 0.01), better mean retinal sensitivity (p = 0.003), higher fixation quality scores, and higher fixation location percentage (p = 0.008) before surgery were prone to get continuous IS/OS junction 12 months after surgery. CONCLUSIONS: MP-1 exams evaluate the dysfunctional hole margin and thus provide more comprehensive information of the preoperative visual function of IMH patients. Both mean retinal sensitivity and fixation behaviors are ideal measurements in predicting the prognosis after successful macular hole surgery.

Predictive Assessment of Quantitative Ultra-Widefield Angiographic Features for Future Need for Anti-VEGF Therapy in Diabetic Eye Disease.

The objective of this study was to identify biomarkers that predict a future need for anti-VEGF therapy in diabetic retinopathy (DR). Eyes with DR that underwent ultra-widefield angiography (UWFA) and had at least a 1 year follow-up were grouped based on future anti-VEGF treatment requirements: (1) not requiring treatment, (2) immediate treatment (within 3 months of UWFA), and (3) delayed treatment (after 3 months of UWFA). Quantitative UWFA features and clinical factors were evaluated. Random forest models were built to differentiate eyes requiring immediate and delayed treatment from the eyes not requiring treatment. A total of 173 eyes were included. The mean follow-up was 22 (range: 11-43) months. The macular leakage index, panretinal leakage index, presence of DME, and visual acuity were significantly different in eyes requiring immediate (n = 38) and delayed (n = 34) treatment compared to eyes not requiring treatment (n = 101). Random forest model differentiating eyes requiring immediate treatment from eyes not requiring treatment demonstrated an AUC of 0.91 ± 0.07. Quantitative angiographic features have potential as important predictive biomarkers of a future need for anti-VEGF therapy in DR and may serve to guide the frequency of a follow-up.

Endoscopic transethmoidal and transconjunctival inferior fornix approaches for repairing the combined medial wall and orbital floor blowout fractures.

PURPOSE: To assess the combination of an endoscopic transethmoidal approach (ETEA) and a transconjunctival inferior fornix approach (TIFA) for repairing combined orbital floor and medial wall blowout fractures (COF-MWBOFs). METHODS: Patients with unilateral COF-MWBOFs were randomized to 2 groups: ETEA combined with TIFA or medial canthal incision (MCI) combined with TIFA. Thin porous polyethylene sheets were implanted to cover the orbital defects. The postoperative follow-up time was 6 months. For both groups, degree of diplopia, enophthalmos, ocular motility, and complications were recorded and compared. RESULTS: Our study included 32 patients in the ETEA group and 27 patients in the MCI group. The time from trauma to surgery ranged from 10 to 48 days. The herniated orbital contents were completely reduced in 96.9% (31/32) of the ETEA group and in 77.8% (21/27) of the MCI group (P=0.040). At the 6-month review, the success rate of enophthalmos correction in the ETEA group achieved 96% (24/25), higher than that in the MCI group (66.7%, 12/18; P=0.015). The improvement of the enophthalmos was better in the ETEA group than in the MCI group (4.5±0.7 mm versus 3.2±1.2 mm) at 6 months (P=0.000). We found no difference in the resolution rate of diplopia within a 30-degree visual field or extraocular muscle function between the 2 groups. Complications in the MCI group included 1 patient with optic neuropathy after the procedure and 4 patients with medial canthal webbing. CONCLUSIONS: Endoscopic transethmoidal approach combined with TIFA is a promising technique for repairing extensive COF-MWBOFs.

Correlation of LINE-1 Hypomethylation With Size and Pathologic Extent of Dysplasia in Colorectal Tubular Adenomas.

INTRODUCTION: Conventional adenomas (tubular adenoma [TA] or tubulovillous adenoma) and sessile serrated lesions (SSLs) are neoplastic precancerous lesions frequently detected in patients undergoing average risk screening colonoscopy and polyp surveillance. Metachronous risk stratification of adenomas is currently limited to histologic features and size of polyps. We report long interspersed nucleotide element-1 (LINE-1) methylation levels in SSL in comparison to TA and the impact of TA size and presence of high-grade dysplasia (HGD) on LINE-1 methylation. METHODS: LINE-1 methylation was assessed by pyrosequencing of bisulfite-converted DNA. We compared LINE-1 methylation between TA and SSL, among varying sizes of TA, and between TA with HGD and low-grade dysplasia (LGD). RESULTS: LINE-1 methylation declined with increasing polyp size in TA when comparing those <5 mm (72.31 ± 6.11), 5 to <10 mm (67.50 ± 7.00), and ≥10 mm (66.75 ± 11.89). There were lower LINE-1 methylation levels in TA with LGD (n = 119) compared with SSLs (n = 29) (69.11 ± 8.62 vs 81.41 ± 2.43, P < 0.001). TA containing HGD (n = 26) had lower LINE-1 methylation levels than those with LGD (n = 119) (59.86 ± 7.93 vs 69.11 ± 8.62, P < 0.001). DISCUSSION: HGD and increasing size of TA/tubulovillous adenoma were associated with lower LINE-1 methylation. This supports a hypothesis that LINE-1 hypomethylation in TAs indicates advancement along the CRC tumorigenesis pathway. Lower LINE-1 methylation and greater variance of global DNA methylation was seen in TA compared with SSL. LINE-1 methylation in adenomas correlates with polyp size and degree of dysplasia and deserves further study as a predictor of metachronous colorectal cancer risk.

Assessing Anorectal Function in Constipation and Fecal Incontinence.

Constipation and fecal incontinence are commonly encountered complaints in the gastrointestinal clinic. Assessment of anorectal function includes comprehensive history, rectal examination, and prospective stool diary or electronic App diary that accurately captures bowel symptoms, evaluation of severity, and quality of life of measure. Evaluation of a suspected patient with dyssynergic constipation includes anorectal manometry, balloon expulsion test, and defecography. Investigation of a suspected patient with fecal incontinence includes high-resolution anorectal manometry; anal ultrasound or MRI; and neurophysiology tests, such as translumbosacral anorectal magnetic stimulation or pudendal nerve latency. This article provides an approach to the assessment of anorectal function.

Quantitative Ultra-Widefield Angiographic Features and Associations with Diabetic Macular Edema.

PURPOSE: To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms. DESIGN: Retrospective image analysis study. PARTICIPANTS: Eyes with diabetic retinopathy that had undergone spectral-domain OCT, UWFA, and ultra-widefield fundus photography. METHODS: OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid. Using a semiautomated analysis platform, UWFA images were segmented for ischemia, leakage, and microaneurysms with manual correction as needed. Clinical variables, including age, gender, race, hemoglobin A1C levels, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status also were evaluated. MAIN OUTCOME MEASURES: Factors associated with the presence and severity of DME. RESULTS: A total of 304 eyes (156 right eyes, 148 left eyes) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, microaneurysm count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular microaneurysms and macular leakage index values revealed that eyes with DME showed a significantly higher microaneurysm count (P = 0.001) and leakage index (P < 0.0001) in the posterior pole compared with eyes without DME. Severity of macular thickening (i.e., CST) was associated significantly with macular leakage index and posterior pole microaneurysm count (P = 0.0002 and P = 0.03, respectively). In addition to posterior pole leakage index and microaneurysm count, DME was associated with older age (P < 0.01), higher systolic blood pressure (P < 0.001), and white race (P = 0.03). Multivariate assessment confirmed the independent association of presence of DME with macular leakage index and macular microaneurysm count (P < 0.01). CONCLUSIONS: Quantitative measures of leakage index and microaneurysm count in the posterior pole on UWFA images were associated with the presence and severity of DME. Panretinal analyses were not linked to DME as strongly. Additional research is needed to determine the role of quantitative UWFA in predicting DME development and characterizing patient prognosis.

MDR1/P-gp and VEGF synergistically enhance the invasion of Hep-2 cells with multidrug resistance induced by taxol.

BACKGROUND: Tumor invasion/metastasis and multidrug resistance (MDR) are the main causes of treatment failure and high mortality in all kinds of cancer patients. The relationship between the two factors is still unclear. The aim of this study is to investigate the association between MDR and invasion, especially the role of multidrug resistance 1/P-glycoprotein (MDR1/P-gp) and vascular endothelial growth factor (VEGF) during the invasion. METHODS: Multidrug resistance 1 (MDR1) and VEGF receptor 2 (VEGFR-2) were detected with real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting at the levels of messenger RNA (mRNA) and protein, respectively. RNA interference was applied to inhibit the expression of MDR1. The invasive assays were performed with the CHEMICON cell invasion assay kit. RESULTS: The MDR cell line induced by Taxol (Hep-2T cell) was more invasive than its parent cell line (Hep-2 cell), which was at least in part mediated through the overexpressed MDR1/P-pg. MDR1-targeted RNA interference could effectively inhibit the expression of MDR1 and obviously decrease the invasive ability. Synergistic enhancing effects existed between MDR1/P-gp and VEGF on the invasion of Hep-2T cells. The expression of VEGFR-2 was elevated in Hep-2T cells. SU1498 could significantly decrease the invasion of Hep-2T cells. MDR1-targeted RNA interference and SU1498 had synergistic decreasing effect on the invasion of Hep-2T cells. CONCLUSIONS: MDR1/P-pg may be a risk predictor for the invasion of laryngeal cancer. MDR1 knock down and VEGFR-2 inhibitor may be two promising treatment regiments for advanced laryngeal carcinoma patients with MDR and invasion/metastasis.

Primary treatment of acute dacryocystitis by endoscopic dacryocystorhinostomy with silicone intubation guided by a soft probe.

PURPOSE: To investigate the suitability of cold steel endonasal endoscopic dacryocystorhinostomy (EES-DCR) with circular bicanalicular intubation with silicone tubes (CBIST) guided by a soft probe for the primary treatment of acute purulent dacryocystitis (APD). DESIGN: Prospective, randomized, interventional case series. PARTICIPANTS: Seventy-two patients (59 females, 13 males) with a median presenting age of 55+/-12 years (range, 28-71 years). METHODS: Eighty-four patients with unilateral APD were equally and randomly divided into 2 groups. Cold steel EES-DCR was performed after the lacrimal abscess formation, and external dacryocystorhinostomy (E-DCR) was performed 1 to 2 weeks after resolution of the acute inflammation. In both groups, CBIST guided by a soft probe was performed and the silicone tubes were kept in the lacrimal passages for 3 months. Postoperative follow-up ranged from 12 to 24 months. Outcomes were compared between both groups, considering resolution time for external acute inflammation, success rate of free lacrimal passage reconstruction, and lack of complications as indicators of treatment suitability. MAIN OUTCOME MEASURES: Time for resolution of the external acute inflammation, success rate of free lacrimal passage reconstruction, and complications. RESULTS: In this study, complete postoperative data were acquired from 40 patients in the EES-DCR group and from 32 patients in the E-DCR group, and the outcomes were compared. Acute inflammation resolved more quickly in the EES-DCR group than in the E-DCR group (P<0.05). Ostium patency at 12 months after silicone tube removal was achieved in significantly more patients in the EES-DCR group (36/40 [90%]) than in the E-DCR group (21/32 [65.7%]; P<0.01). In the EES-DCR group, lacrimal passage reconstruction failed because of intranasal ostial closure in 3 patients and because of common canaliculus obstruction in 1 patient. In the E-DCR group, lacrimal passage reconstruction failed because of intranasal ostial closure in 3 patients, lacrimal sac fibrosis, granulation, or both in 6 patients, and common canaliculus obstruction in 2 patients. Other than the slight laceration of the inferior puncta, no significant complications arose from the treatments. CONCLUSIONS: Cold steel EES-DCR with CBIST guided by a soft probe is a promising alternative for the primary treatment of APD with abscess formation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

The characteristics of Hep-2 cell with multiple drug resistance induced by Taxol.

OBJECTIVE: To investigate the characteristics of Hep-2 cell with multidrug resistance (MDR) induced by Taxol. STUDY DESIGN: Hep-2 cells were exposed in stepwise escalating concentration of Taxol to develop the resistant cell line-Hep-2T. Cell cycle distribution, apoptosis, and rhodamine accumulation were studied through flow cytometry. The MDR1 and MRP1 genes were detected through real-time quantitative RT-PCR, and the corresponding proteins were detected through Western blotting. RESULTS: The drug resistance of Hep-2T cells to Taxol, doxorubicin, gemcitabine, 5-FU, and cisplatin all increased. The percentage of G0/G1 phase and the antiapoptosis ability increased significantly compared with Hep-2 cells. Both MDR1 and MRP1 also increased at gene and protein level, though MDR1 was more prominent. CONCLUSION: More emphasis should be laid on MDR1/Pgp, the non-Pgp substrate chemotherapeutic agents, and the changes of cell cycle distribution to prevent MDR induced by Taxol. SIGNIFICANCE: These findings may provide theoretical support for the reverse of MDR.

Effect of bovine lactoferrin from iron-fortified formulas on diarrhea and respiratory tract infections of weaned infants in a randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effect of supplementation with bovine lactoferrin (bLf) from iron-fortified formulas on diarrhea and respiratory tract infections (RTIs) in weaned infants. METHODS: In this prospective, multicenter, controlled intervention study, 260 infants ages 4 to 6 mo who previously were exclusively breastfed but weaned were randomized into two groups: a lactoferrin-fortified formula milk group (fortified group, FG, containing lactoferrin 38 mg/100 g milk) and a no lactoferrin-fortified milk (control group, CG); breastfed infants were enrolled and served as a reference group (breastfed group, BG). The intervention duration was 3 mo. The morbidity of diarrhea and RTIs were collected during supplementation. RESULTS: The results of the study demonstrated evidence of a lower incidence rate of respiratory-related illnesses and fewer symptoms of running nose, cough, and wheezing for infants in the FG and BG groups compared with those in the CG (P < 0.05). Despite the undistinguished incidence rate of vomiting, nausea, and colic, the occurrences of diarrhea-related illnesses were significantly lower for children in the FG and BG than for those in CG (P < 0.05). CONCLUSION: The beneficial effects on infectious morbidity over 3 mo highlighted the potential of bLF supplementation for previously weaned infants; these findings may be applicable to other infants living in similar socioeconomic districts.

ERK1/2 signaling pathway in the release of VEGF from Müller cells in diabetes.

PURPOSE: Diabetic retinopathy (DR) is one of the most serious complications of diabetes and has become a major blinding eye disease, but its treatment remains unsatisfactory. The ERK1/2 signaling pathway has been shown to participate in regulating secretion of VEGF in DR from our previous studies. The role of VEGF in the development of DR provides a target for treatment. Our present research focuses on Müller cells, a major source of VEGF secretion, to investigate the role of ERK1/2 signaling pathway on regulation of VEGF release in diabetes. METHODS: Immunofluorescence was used to observe the ERK1/2 phosphorylation activity on early diabetic rat retinal Müller cells. Müller cells were stimulated by high glucose in vitro. Western blot and immunohistochemistry were used to determine ERK1/2 signaling pathway expression and phosphorylation. AP-1 DNA binding activity status was monitored by electrophoretic mobility shift assay (EMSA). ELISA and PCR monitored VEGF secretion. Inhibition of ERK1/2 phosphorylation with U0126 was observed for changes in VEGF secretion. RESULTS: Phos-ERK1/2 was expressed on Müller cells early in diabetes. In vitro high glucose stimulation of Müller cells increased VEGF secretion with a peak at 24 hours. An ERK1/2 specific inhibitor, U0126, stopped the phosphorylation of ERK1/2, lowered AP-1 DNA binding activity, and reduced Müller cells secretion of VEGF under high glucose conditions. CONCLUSIONS: ERK1/2 signaling pathway has some role in regulating Müller cells secretion of VEGF in DR. Targeting the ERK1/2 signaling pathway in Müller cells through intervention of the upstream signaling pathway or nuclear transcription factors of VEGF secretion could be a type of anti-VEGF treatment for DR.

ERK1/2 signaling pathways involved in VEGF release in diabetic rat retina.

PURPOSE: Vascular endothelial growth factor (VEGF) is one of the major factors promoting diabetic retinopathy (DR). A better understanding of the signaling pathway in VEGF regulation is of clinical importance to identify more precise therapeutic targets for diabetic retinopathy. The ERK1/2 signaling pathway has been shown to play a key role in some oncoma and hematologic diseases by mediating VEGF release. This research was conducted to determine whether the ERK1/2 signaling pathway also plays a major role in VEGF release in DR development. METHODS: One hundred Sprague-Dawley (SD) rats were induced to diabetes by streptozotocin (STZ) injection and monitored at several time points (1, 2, 3, 4, 8, and 12 weeks) for ERK1/2 phosphorylation, Activator protein (AP)-1 activity and concentration, and VEGF protein and mRNA expression, using immunohistochemical and biochemical methods. RESULTS. The ERK1/2 signaling pathway was rapidly activated 1 week after diabetes was induced. AP-1, the downstream transcription factor of ERK1/2, was also activated, and VEGF became highly regulated in a similar trend. U0126, an inhibitor of ERK1/2, also downregulated VEGF expression, in addition to ERK1/2 and AP-1 activity. CONCLUSIONS: ERK1/2 signaling pathway is involved in VEGF release in diabetic rat retina; therefore, ERK1/2 may be a potential therapeutic target of DR.

The analysis of tear meniscus in soft contact lens wearers by spectral optical coherence tomography.

PURPOSE: To evaluate the changes of tear meniscus in eyes fitted with soft contact lens (SCL) by spectral optical coherence tomography (SOCT). METHODS: Thirty-three contact lens wearers who wore daily-wear frequent-replacement SCL with 55% water content for more than 6 years on average, and 33 normal subjects were enrolled in this study. The meniscus at the central lower lid of the left eye was examined by SOCT. For the lens wearers, the examination was performed twice: once with contact lens and once without. For the non-lens wearers, the examination was performed only once. The image of lower tear meniscus was divided into two parts: the hyperreflective curved layer (P1) and the hyporeflective triangular area (P2). The height of P1 and P2 (H-P1 and H-P2) was measured, along with the thickness and area of both parts (T-[P1+P2] and A-[P1+P2]). RESULTS: The cornea, lower eyelid, contact lens, and the lower tear meniscus could be clearly visualized in the SOCT images. For the lens wearers, the mean values of H-P1, H-P2, T-[P1+P2], and A-[P1+P2] measured before removing the lenses were 164.18 +/- 41.77 microm, 148.6 +/- 42.84 microm, 134.72 +/- 38.39 microm, and 9914 +/- 469 microm. The values of these parameters measured after lens removal showed no significant differences from those measured with the lens. Variables tested in lens-wearers with and without contact lenses were both significantly lower than those of normal subjects. CONCLUSIONS: SOCT can be helpful in evaluation of the lower tear meniscus in the eye fitted with a SCL. Long-term SCL wear could induce decreased tear volume, especially by reduction of the aqueous component.