Recalled age of myopia onset may predict risk of high adult myopia in Chinese adults.

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

Circ_0000291 contributes to hepatocellular carcinoma tumorigenesis by binding to miR-1322 to up-regulate UBE2T.

INTRODUCTION AND OBJECTIVES: Circular RNAs (circRNAs) are identified to show important regulatory functions in cancer biology. We attempted to analyze the role of circ_0000291 in hepatocellular carcinoma (HCC) progression and its related mechanism. METHODS: The circular characteristic of circ_0000291 was tested using exonuclease RNase R. Cell proliferation was analyzed by 5-Ethynyl-2'-deoxyuridine (EdU) incorporation and colony formation assays. Cell apoptosis was measured by flow cytometry and a caspase 3 activity assay kit. Transwell assays were performed to analyze cell migration and invasion abilities. Sphere formation assay was conducted to analyze cell stemness. Dual-luciferase reporter and RNA-pull down assays were conducted to verify the interaction between microRNA-1322 (miR-1322) and circ_0000291 or ubiquitin conjugating enzyme E2 T (UBE2T). RESULTS: Circ_0000291 was markedly up-regulated in HCC tissues and cell lines. HCC patients with high expression of circ_0000291 displayed a low survival rate. Circ_0000291 knockdown restrained the proliferation, migration, invasion, and stemness and induced the apoptosis of HCC cells. Circ_0000291 directly interacted with miR-1322 and negatively regulated miR-1322 expression. Circ_0000291 knockdown-mediated anti-tumor impacts in HCC cells were largely overturned by the interference of miR-1322. miR-1322 directly paired with the 3' untranslated region (3'UTR) of UBE2T, and UBE2T was negatively regulated by miR-1322. UBE2T overexpression largely reversed circ_0000291 silencing-induced effects in HCC cells. Circ_0000291 positively regulated UBE2T expression by absorbing miR-1322 in HCC cells. Circ_0000291 silencing notably reduced the tumorigenic potential in vivo. CONCLUSION: Circ_0000291 facilitated HCC progression by targeting miR-1322/UBE2T axis, which provided novel potential biomarkers and targets for HCC patients.

Cellular Blue Nevus of Perilimbal Conjunctiva: A Case Report and Review of Literature.

Cellular blue nevus is an uncommon neoplasm in the conjunctiva. Here we present an unusual case of a cellular blue nevus that clinically resembled conjunctival melanoma. A 29-year-old Chinese male was found to have a giant pigmented lesion of the conjunctiva around the limbal area of right eye from birth. Excisional biopsy with no-touch technique, lamellar corneal transplantation, amniotic membrane transplantation and adjuvant cryotherapy were performed. Histopathology revealed a nodular, well-defined tumor, which was composed of heavily pigmented dendritic cells and less pigmented spindle cells. There was no recurrence during eight years follow-up. Cellular blue nevus of conjunctiva can be wrongly diagnosed as conjunctival melanoma due to atypia criteria. Therefore, it is important to understand its clinical and pathological characteristics to avoid an overtreatment.

Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells.

PURPOSE: Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment. MATERIALS AND METHODS: The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed. The viability of bladder cancer cells BIU-87 and EJ was determined by MTT assay. The apoptotic assay was demonstrated by flow cytometry and TEM. Virus titer was determined by TCID50 assay, and proteins Mre11, Chk2-Thr68, and E1A were analyzed by Western blot method. RESULTS: Oncolytic adenovirus combined with radiotherapy improved antitumor efficacy compared with the single treatment at a time and was X-ray dosage-dependent. When the adenovirus infection was scheduled at 24 h after irradiation, cancer cells had the lowest viability. Adenovirus and irradiation induced cell death through the caspase-3 related apoptotic pathway, and bladder cancer cells were arrested at the G1 (BIU-87) or S phase (EJ). Autophagic vacuoles were observed in bladder cancer cells treated with radiation and adenovirus. After irradiation, more virus particles were observed in the BIU-87 and EJ cells. However, by a TCID50 assay, there was no difference in virus titter between irradiated bladder cancer cells and unirradiated cells. The proteins Mre11, Chk2-Thr68 which involved in the DNA break repair pathway were decreased while γ-H2AX-Ser139 increased; at the same time, the E1A gene and the hexon proteins of oncolytic adenovirus were increased after irradiation. CONCLUSIONS: Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer.

Changes in TL1A levels and associated cytokines during pathogenesis of diabetic retinopathy.

Tumor necrosis factor (TNF) ligand related molecule 1A (TL1A), also termed TNF superfamily member 15 and vascular endothelial growth inhibitor is important for tumorigenicity and autoimmunity. However, the function of TL1A in diabetic retinopathy (DR) remains to be elucidated. The present study established a diabetes mellitus (DM) rat model to investigate TL1A, vascular endothelial growth factor (VEGF), tumor necrosis factor­α (TNF­α) and interleukin­1ß (IL­1ß) expression levels in the retina, vitreous and serum of rats with DM at different stages (1 month group, 3 month group and 6 month group). The present study determined that TL1A expression levels in the retina and vitreous from the DM 1 month group were significantly lower compared with the control group. However, TL1A levels in the retina and vitreous were significantly increased in advanced stages of DM compared with the control group. Furthermore, the levels of VEGF in the retina and vitreous were significantly higher in the DM groups compared with the control group. The expression levels of TNF­α and IL­1ß in the retina and vitreous were significantly higher in DM 3 month and 6 month groups compared with the control group. It is of note that the expression levels of TL1A were significantly lower in the DM 1 and 3 month groups compared with the control group; however, they were significantly increased in the DM 6 month group compared with the DM 3 month group. The expression levels of VEGF, TNF­α and IL­1ß in blood serum have been observed to exhibit similar expression change dynamics as those of the retina and vitreous. Therefore, these findings suggest that TL1A may be a protective factor of DR, and may provide a rationale for the development of novel therapeutic strategies to treat DR.

TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes.

Tumor necrosis factor superfamily 15 (TNFSF15) is an endogenous neovascularization inhibitor and an important negative regulator of vascular homeostasis. This study aimed to explore the potential role of TNFSF15 in diabetic retinopathy. Vitreous TNFSF15 and VEGF levels in proliferative diabetic retinopathy (PDR) patients were detected by ELISA. Retinal expression of TNFSF15 and the content of tight junction proteins (TJPs) in rats were detected by immunohistochemistry and Western blot, respectively. The blood retinal barrier (BRB) permeability was evaluated using Evans Blue (EB) dye. The TNFSF15/VEGF ratio was decreased in the vitreous fluid of patients with PDR relative to the controls, even though the expression levels of TNFSF15 were higher. TNFSF15 was dramatically decreased one month later after diabetes induction (p < 0.001), and then increased three months later and thereafter. TNFSF15 treatment significantly protected the BRB in the diabetic animals. Diabetes decreased TJPs levels in the retina, and these changes were inhibited by TNFSF15 treatment. Moreover, TNFSF15 decreased activation of VEGF both in mRNA and protein levels caused by diabetes. These results indicate that TNFSF15 is an important inhibitor in the progression of DR and suggest that the regulation of TNFSF15 shows promise for the development of diabetic retinopathy treatment strategies.

Vitreous and plasma VEGF levels as predictive factors in the progression of proliferative diabetic retinopathy after vitrectomy.

PURPOSE: To investigate the vitreous and plasma levels of vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR) and to determine whether they predict a disease prognosis after primary vitrectomy. METHODS: Fifty patients (50 eyes) with PDR who underwent pars plana vitrectomy (PPV) and 56 healthy controls (56 eyes) were enrolled in this retrospective study. Clinical data were collected and analyzed. Vitreous and plasma VEGF concentrations were measured using enzyme-linked immunosorbent assays. VEGF levels and clinical data were compared and analyzed to see if they provide a prognosis of PDR progression after primary vitrectomy at more than 6 months follow-up. Correlation of VEGF concentrations between vitreous fluid and plasma was analyzed. RESULTS: The average BCVA was significantly improved after surgery (P<0.001). Vitreous and plasma VEGF levels were significantly elevated in PDR patients than those in healthy controls (P vitreous<0.001; P plasma<0.001). Both vitreous and plasma VEGF levels were significantly higher in PDR progression group than in stable group (P vitreous < 0.001; P plasma = 0.004). Multivariate logistic regression analyses showed that the increased vitreous VEGF level was associated with the progression of PDR after primary PPV (OR = 1.539; P = 0.036). Vitreous VEGF level was positively associated with plasma VEGF level in PDR patients (P<0.001). CONCLUSION: The increased VEGF level in vitreous fluid may be identified as a significant predictive factor for the outcome of vitrectomy in patients with PDR.

Roles of elevated intravitreal IL-1ß and IL-10 levels in proliferative diabetic retinopathy.

PURPOSE: To determine the roles of interleukin (IL)-1ß and IL-10 in the vitreous of proliferative diabetic retinopathy (PDR). MATERIALS AND METHODS: Vitreous samples were obtained from 26 eyes of 26 patients with PDR and from eight eyes of eight cases without PDR. The IL-1ß and IL-10 concentration in the vitreous was measured by using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Levels of IL-1ß and IL-10 in vitreous were higher in PDR patients compared with control group. And there was significantly negative correlation between IL-1ß and IL-10 in control group (r = -0.795; P = 0.032), whereas there was no significant correlation in PDR group (r = 0.176; P = 0.391). CONCLUSION: Levels of IL-1ß and IL-10 were upregulated in vitreous of PDR patients, and these two cytokines play roles in regulating the development and progression of PDR.

[Clinical characteristics of mechanical ocular injury and application of ocular trauma score].

OBJECTIVE: To summarize clinical characteristics of mechanical ocular injury and to analyze the role of ocular trauma score (OTS) in the estimation of final visual acuity. METHODS: All cases of ocular trauma admitted to the Department of Ophthalmology from January 2009 to December 2010 were retrospectively reviewed. Data extracted included laterality of the injured eye, gender, age, presenting time, cause, ocular trauma classification, initial and final visual acuity. These injuries were classified by ocular trauma classification system (OTCS). We also used the OTS in evaluating the final visual outcome. Comparisons between groups for discontinuous variables were analyzed using rank-sum test. Rank correlation was used in analysis between initial visual acuity and final visual acuity or between final visual acuity and OTS. Chi-square test was used to analyze variables, such as age, cause, type and visual acuity. Comparison of ages between male and female was analyzed by using t-test. RESULTS: Of the 168 eyes, there were 106 open globe injury (OGI) and 62 closed globe injury (CGI). There were 140 males (85.71%) and 22 females (14.29%). Presenting time median of OGI and CGI was 5 h and 10 h respectively, and there was significant difference between these two different injuries (Z = -2.547, P = 0.011). The high-risk age group was the young age group (100 eyes, 59.52%), vs. the middle age group (46 eyes, 27.38%) and the elder age group (22 eyes, 13.10%). Occupation-related injury (70 eyes) was the most common cause and mainly resulted in OGI (54/70). Initial and final visual acuities in CGI were better than those of OGI (χ(2) = 37.847, P = 0.000; χ(2) = 44.428, P = 0.000). Initial visual acuity was correlated with final visual acuity (r = 0.858, P = 0.000). Final visual acuity was significantly correlated with total score (r = 0.870, P = 0.000) and OTS (r = 0.869, P = 0.000). CONCLUSIONS: In this group of mechanical ocular trauma patients, male is more common than the female. Main type of injury is OGI and presenting time of OGI is earlier than that of CGI. The high-risk age group is the young. Main cause of injury is occupation-related injury. Initial and final visual acuities in CGI are better than those in OGI. OTS calculated at initial examination may be a useful parameter for the estimation of prognosis.

[Retinal cell apoptosis, microvascular changes and expression of connective tissue growth factor in experimental diabetic rats].

OBJECTIVE: To study the cell apoptosis and the expression of connective tissue growth factor (CTGF) in the retina of diabetic rats and to explore their contributions to the changes of microcirculation. METHODS: It was a experiment study. Fifty-five adult male Wistar rats were divided into two groups, normal control group (CON, 10 rats) and diabetes mellitus group (DM, 45 rats). The 30 surviving rats in the DM group were further divided into 3 groups based on the time of observation, 2 month (DM2), 4 month (DM4) and 6 month (DM6) groups, with 10 rats in each group. Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). Expression of CTGF was determined by immunohistochemical study. Retinal vessels were observed by retinal digest stretched periodic acid Schiff (PAS) staining. RESULTS: Immunohistochemical staining and TUNEL staining revealed negative results in normal control group. Retinal cell apoptosis index increased gradually from DM2 to DM6, the differences between any two groups were statistically significant (t(2-4, 2-6, 4-6) = 21.432, 50.843, 29.410; P < 0.05). Expression of CTGF in the retina increased from DM2-DM6, the differences between any two groups were statistically significant (t(2-4, 2-6, 4-6) = 15.345, 26.316, 10.971; P < 0.05). PAS staining of retinal blood vessels obtained negative results in the CON and DM2 groups. Part of retinal capillaries were slightly stiff and narrow in DM4 group. Retinal capillaries in DM6 group were trunk stiff and were narrowed obviously. The number of pericytes was reduced in DM4, and progressed following the course of diabetes. The number of pericytes in the DM2 group did not different from that in the CON group (t = 0.875, P = 0.387). The number of pericytes in the DM4 and DM6 group were significantly decreased as compared to the CON group (t = 3.367, 6.667; P < 0.05). Retinal cellular apoptosis index had a significant positive correlation to the expression of CTGF (r = 0.958, P < 0.05). Number of pericytes was significantly correlated (negative correlation) with retinal cellular apoptosis index and the expression of CTGF (r = -0.540, -0.595; P < 0.05). CONCLUSIONS: The appearances of cellular apoptosis and fibrosing factor CTGF in the retina of diabetic rats occurred earlier than the changes of microcirculation and the number of capillary pericytes.