Low-Reflectivity Drusen With Overlying RPE Damage Revealed by Spectral-Domain OCT: Hint for the Development of Age-Related Macular Degeneration.

Purpose: To observe the relationship between the characteristic changes in the drusen morphology revealed by the spectral-domain optical coherence tomography (SD-OCT) and the progression of age-related macular degeneration (AMD). Methods: A total of 380 drusen in 45 eyes in 35 patients with the intermediate drusen were longitudinally followed up every 6 months by SD-OCT for a period of 24 months. The drusen were divided into the dynamic group and stable group according to the following parameters: number, volume, concurrent retinal pigment epithelium (RPE)/ellipsoid zone (EZ) damage, and the development of advanced AMD. The morphological characteristics of the progressive or stable drusen were further analyzed. Odds ratios (ORs) and the risk for the drusen progression were calculated. Results: The level of interobserver and intraobserver agreement for each drusen tomographic morphological parameters ranged from 82.7 to 90%. At the end of an average follow-up of 15.92 ± 6.99 months, six patients developed choroidal neovascularization and no patients developed geographic atrophy. Finally, 139 drusen changed and 241 drusen remained stable. The drusen with low reflectivity (p < 0.001; OR: 5.26; 95% CI: 2.24-12.36), non-homogeneity without a core (p < 0.001; OR: 4.31; 95% CI: 2.08-8.92), RPE damage (p < 0.001; OR: 28.12; 95% CI: 9.43-83.85), and the EZ damage (p < 0.001; OR: 14.01; 95% CI: 5.28-37.18) were significantly associated with active change; the drusen with low reflectivity (p = 0.01; OR: 2.95; 95% CI: 1.29-6.75) and decreased overlying RPE reflectivity (p < 0.001; OR: 21.67; 95% CI: 9.20-51.02) were the independent predictors for progression. The drusen with high reflectivity were significantly associated with stabilization (p = 0.03; OR: 0.17; 95% CI: 0.04-0.84). Conclusion: Spectral-domain optical coherence tomography is an optimized, accurate, and efficient method to follow-up the drusen. The intermediate non-exudative AMD prognosis of the patient was most strongly correlated with the drusen reflectivity and disruption of the overlying RPE layer. The drusen with low reflectivity and overlying RPE damage were more likely to progress and required frequent follow-up.

Chemically stable fluorescent anti-counterfeiting labels achieved by UV-induced photolysis of nanocellulose.

Carbon-based fluorescent security labels are effective methods to prevent counterfeiting. However, the properties of poor optical stability, complex and energy-consuming synthesis processes and weak bonding with substrates of carbon-based fluorescent materials limit their application prospects. Here, a novel in situ fluorescent patterning strategy is developed to achieve covert, chemically stable and solvent-tolerant cellulose-based security labels by UV exposure. The unsaturated double bonds as the origin of the fluorescence were generated during the photodegradation process under UV exposure. The fluorescent emission of cellulose-based materials reveals excellent stability under acidic, alkaline, reducing, oxidizing and non-polar solvent environments. These advantages give the cellulose nanofiber based security label fantastic potential applications.

MicroRNA-138 negatively regulates the hypoxia-inducible factor 1α to suppress melanoma growth and metastasis.

Melanoma with rapid progression towards metastasis has become the deadliest form of skin cancer. However, the mechanism of melanoma growth and metastasis is still unclear. Here, we found that miRNA-138 was lowly expressed and hypoxia-inducible factor 1α (HIF1α) was highly expressed in patients' melanoma tissue compared with the paracancerous tissues, and they had a significant negative correlation (r=-0.877, P<0.001). Patients with miRNA-138low/HIF1αhigh signatures were predominant in late stage III/IV of melanoma. Further, bioinformatic analysis demonstrated that miRNA-138 directly targeted HIF1α. We found that the introduction of pre-miRNA-138 sequences to A375 cells reduced HIF1α mRNA expression and suppressed cell proliferation, migration and invasion. Overexpression of miRNA-138 or inhibition of HIF1α significantly suppressed the growth and metastasis of melanoma in vivo Our study demonstrates the role and clinical relevance of miRNA-138 and HIF1α in melanoma cell growth and metastasis, providing a novel therapeutic target for suppression of melanoma growth and metastasis.

miR-186 suppressed CYLD expression and promoted cell proliferation in human melanoma.

Previous studies have shown that microRNA-186 (miR-186) is overexpressed in various human cancers and is associated with the regulation of the carcinogenic processes. However, the underlying mechanisms of this microRNA in melanoma remain largely unknown. In the present study, the overexpression of miR-186 was identified in melanoma tissues and melanoma cells compared to the expression of miR-186 in the matched tumor adjacent tissues and normal human epidermal melanocytes. Overexpression of miR-186 promoted the proliferation and anchorage-independent growth of melanoma cells, whereas inhibition of miR-186 reduced this effect. Bioinformatics analysis also revealed cylindromatosis (CYLD), a putative tumor suppressor, to be a potential target of miR-186. Luciferase reporter assays showed that miR-186 directly targeted the 3'-untranslated regions of CYLD messenger RNA. Additional experiments showed that overexpression of miR-186 promoted the proliferation of melanoma cells, which was consistent with the inhibitory effects induced by knockdown of CYLD. In summary, the present study indicated that miRNA-186 plays a crucial role in melanoma growth and its oncogenic effect is mediated chiefly through the direct suppression of CYLD expression.

MiR-769 promoted cell proliferation in human melanoma by suppressing GSK3B expression.

MicroRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory function, playing crucial roles in cancer development and progression of human melanoma. Previous studies have indicated that miR-769 was implicated in diverse biological processes. However, the underlying mechanism of miR-769 in human melanoma has not been intensively investigated. In this present study, we aimed to investigate the role of miR-769 and its target genes in human melanoma. We found that miR-769 expression was strongly increased in human melanoma cells and clinical tissues compared with their corresponding controls. Overexpression of miR-769 promoted cell proliferation in human melanoma cell line A375, whereas miR-769-in reverses the function. Glycogen synthase kinase-3 Beta (GSK3B), a potential target gene of miR-769, and was validated by luciferase assay. Further studies revealed that miR-769 regulated cell proliferation of human melanoma by directly suppressing GSK3B expression and the knockdown of GSK3B expression reversed the effect of miR-769-in on human melanoma cell proliferation. In summary, our data demonstrated that miR-769 might act as a tumor promoter by targeting GSK3B during development of human melanoma.

Inhibition of RelA expression via RNA interference induces immune tolerance in a rat keratoplasty model.

RelA, the most important regulator of NF-kB activity, and its mechanisms in keratoplasty immune rejection have not been fully investigated. In the present study, lentivirus-mediated silencing of RelA expression in a bone marrow-derived dendritic cell (BMDC) model was tested. The BMDCs were transfected with RelA-shRNA to induce an immature, maturation-resistant and tolerogenic phenotype, while not significantly changing IFN-γ, IL-10 and IL-17 expression. A fully allogeneic rat cornea transplant model was established for in vivo studies. The allograft mean survival time (MST) of lv-shRelA-DC injection groups were significantly longer than the untreated BMDC group and control group. The corneal opacity and neovascularization scale of the lv-shRelA-DC injection groups were slight compared to pair control others. Postoperative flow cytometric analysis revealed that the percentage of Treg positive cells was dramatically increased in animals that received an lv-shRelA-DC injection. ELISA and qRT-PCR analyses of serum showed that IFN-γ and IL-17 expression were suppressed by lv-shRelA-DC treatement. In vivo experiments demonstrated that IL-10 induced immunosuppression was partly attributed to injection of lv-shRelA-DC throughout the experiment, differing from the general anti-inflammatory factors. Luciferase and Chromatin IP evaluation showed that RelA knockdown in BMDCs significantly reduces DNA binding to IFN-γ, IL-10 and the IL-17 promoter and inhibited of transcriptional activity. Taken together, this study illustrates a significant role of RelA in mediating the corneal neovascularization by affecting IL-17 expression. Our comprehensive analysis shows that the significant role of RelA provides a novel and feasible therapeutic approach for the prevention of corneal allograft rejection.

Clinicopathological analysis of 39 patients with corneal tumor.

PURPOSE: Corneal tumors are rare in clinical practice. There was a paucity of data on the incidence of various corneal tumors, their clinical and pathological features and surgical management, especially on large patient samples. METHODS: The medical records of 39 patients with corneal tumors referred to Zhongshan Ophthalmic Center, Sun Yat-sen University, China from Jan 1,1996 to Dec 31,2002 were reviewed retrospectively. RESULTS: Of the 39 cases with corneal tumors, 31 were males and 8 were females. The right eye was affected in 24 cases and the left one in 15 cases. The mean age at diagnosis was 45.7 years, ranged from 3 to 88 years. Squamous cell carcinoma was the most common tumor in the cornea (18 cases, 46.15%), followed by pigmented naevus (12 cases,30.77 %), papillary epithelioma (3 cases, 7.69%), melanoma (1 case, 2.56%), oncosis hyperplasia(1 case, 2.56%) , inverting papilloma (1 case, 2.56%）, primary acquired melanosis (1 case, 2.56%) amyloid degeneration (1 case, 2.56%) inflammatory pseudotumor (1 case, 2.56%）. They arose most commonly in the limbal region. All tumors were unilaterally involved. Squamous cell carcinoma of the cornea usually appears as a whitish, rough, irregular lesion or a telangiectatic, gelatinous epibulbar mass. Nevus in the cornea generally becomes clinically apparent in the first or second decade of life and the lesion may enlarge or more deeply pigmented afterwards. The corneal tumors were completely excised microsurgically in 22 cases. Six cases were treated with surgical resection combined with amniotic membrane graft. Three cases with surgical excision plus transfer of conjunctival flap. Two cases with surgical excision plus lamellar keratoplasty. Two cases with surgical excision plus cryosurgery. Two cases with orbital exenteration. One case with enuleation. One case with incision biopsy and observation. CONCLUSION: Squamous cell carcinoma and nevus, the most common corneal tumors, accounted for 76.92% of all cases. The therapeutic outcomes depended upon early pathologic diagnosis and early surgical management.

Immunohistochemical study of the presence of mast cells in idiopathic orbital inflammatory pseudotumor: possible role of mast cells in the course of its pathogenesis.

BACKGROUND: It is well known that mast cells (MC) are involved in fibrosis and many forms of chronic inflammation. Chronic inflammatory cells infiltration and fibrosis in various orbital tissues are the main histopathologic features in patients with idiopathic orbital inflammatory pseudotumor (IOIP). Whether MC is involved in the course of chronic inflammatory conditions of IOIP is not yet clear. We sought to investigate the distribution of MCs in samples of IOIP and to explore the possible role of MC in the course of its pathegenesis. METHODS: Immunohistochemistry with tryptase monoclonal antibody (a specific mast-cell surface marker) was used in 53 different subtypes of IOIP specimens including 19 of the lymphocyte infiltrative type, 22 of the fibrotic type, 12 of the mixed type and 4 specimens of normal orbital tissue. The number of positive stained MC was counted by light microscopy. The differences of the number of MC between various subtypes of IOIP were analyzed. RESULTS: The average number of positive stained MC in the normal control group was 33.33 +/- 4.72 /mm(3), whereas the average numbers of positive stained MC in the lymphocyte infiltrative subtype group, the mixed subtype group and the fibrotic subtype group were 306.35 +/- 55.81 /mm(3), 662.93 +/- 115.28 /mm(3) and 813.44 +/- 146.56 /mm(3), respectively. Compared with the normal control, the number of MC increased significantly in all three subtypes of IOIP samples (P < 0.01). The number of MC in fibrotic subtype IOIP was the largest, followed by mixed subtype IOIP, and the lymphocyte infiltrative subtype IOIP (P < 0.05). The MC were distributed mainly around small vessels and in collagen fibers. CONCLUSION: Mast cells may play an underappreciated role in the fibrosis of IOIP.

Idiopathic orbital inflammatory pseudotumor in Chinese children.

PURPOSE: To study the clinical features of idiopathic orbital inflammatory pseudotumor (IOIP) in Chinese children. METHODS: Pediatric patients with IOIP seen between Jan. 1, 1978 and Dec. 31, 1999 in the Eye Hospital, Zhongshan Ophthalmic Center, Sun Yat-sen University were evaluated retrospectively. Their clinical features were compared with those of adult cases of IOIP. RESULTS: Of the 209 cases, 24 (11.5%) were equal to or less than 20 years old; 14 were female and 10 were male. There were 11 in the right eye, 9 in the left eye and 4 in both eyes. Palpable mass (58%), ocular motility restriction (46%), swollen eyelid (42%), proptosis (42%) and high orbital pressure (42%) were the five most common presenting signs in children with IOIP. Ptosis occurred more often in pediatric IOIP cases (38%) than in adult IOIP cases (9%) (P < 0.0003). However, compared with adult IOIP cases, pediatric patients showed less proptosis (69% vs. 42%, P = 0.0074). According to radiological and surgical findings, a local mass within the orbit was the most frequent subtype (50%), followed by dacryoadenitis (29%), myositis (8%), perineuritis (4%), eyelid pseudotumor (4%), and diffuse orbital inflammation (4%). The frequency of clinical subtypes in children was similar to that in adults. After systemic corticosteroids, surgical management and local radiotherapy the full recovery response rate was 29% and the total effective rate was 92%. CONCLUSIONS: Pediatric IOIP accounted for 11.5% of all IOIP patients. Pediatric cases had more sign of ptosis and less sign of proptosis than in adult IOIP. The full recovery response rate was low in children with IOIP.