Key Laboratory of Myopia

Shanghai, China

Key Laboratory of Myopia

Shanghai, China
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Lin T.,Fudan University | Lin T.,Key Laboratory of Myopia | Gong L.,Fudan University | Gong L.,Key Laboratory of Myopia
Drug Design, Development and Therapy | Year: 2017

Purpose: To investigate the feasibility of nintedanib, a novel triple angiokinase inhibitor, for inhibiting lymphatic endothelial cell (LEC)-induced lymphangiogenesis in vitro and inflammatory corneal lymphangiogenesis in vivo. Materials and methods: Methylthiazolyldiphenyl-tetrazolium bromide (MTT) test, transwell system, and tube-formation assay were used to evaluate the effects of nintedanib on the proliferation, migration, and tube formation of LECs stimulated by vascular endothelial growth factor-C (VEGF-C), basic fibroblast growth factor (bFGF), or platelet-derived growth factor-BB (PDGF-BB). The murine model of suture-induced corneal neovascularization was used to assess the anti-hemangiogenic and anti-lymphangiogenic effects of nintedanib via systemic and topical applications. Corneal flatmounts were stained with lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and CD31, and the areas of involved blood and lymph vessels were analyzed morphometrically. Corneal cryosections were stained with F4/80 to evaluate inflammatory cell recruitment. Results: We observed a significant enhanced effect of LEC proliferation, migration, and tube formation with the administration of VEGF-C, PDGF-BB, and bFGF, respectively, which was diminished by nintedanib. Both topical and systemic applications of nintedanib inhibited suture-induced hemangiogenesis and lymphangiogenesis in the murine cornea. A reduction in F4/80+ cell infiltration was observed at day 14 after corneal suture for both systemic and topical applications of nintedanib. In comparison with controls, 61% of F4/80+ cell recruitment was inhibited via the systemic application of nintedanib, while 49% of F4/80+ cell recruitment was inhibited with the topical application of nintedanib. Conclusion: Nintedanib was shown to inhibit in vitro lymphangiogenesis stimulated by VEGF-C, bFGF, and PDGF-BB. Applied topically or systemically, it effectively inhibited corneal hemangiogenesis and lymphangiogenesis, accompanied by reduced inflammatory cell recruitment, which represents a new promising treatment for graft rejection after penetrating keratoplasty. © 2017 Lin and Gong.

PubMed | Fudan University, CAS Shanghai Institutes for Biological Sciences and Key Laboratory of Myopia
Type: Journal Article | Journal: Journal of cellular physiology | Year: 2016

Cataractogenesis begins from the dynamic lens epithelial cells (LECs) and adjacent fiber cells. LECs derived from cell lines cannot maintain the crystalline expression as the primary LECs. The current study aimed to efficiently generate large numbers of human LECs from patient-specific induced pluripotent stem cells (iPSCs). Anterior lens capsules were collected from cataract surgery and were used to culture primary hLECs. iPSCs were induced from these primary hLECs by lentiviral transduction of Oct4, Sox2, Klf4, and c-Myc. Then, the generated iPSCs were re-differentiated into hLECs by the 3-step addition of defined factor combinations (Noggin, BMP4/7, bFGF, and EGF) modified from an established method. During the re-differentiation process, colonies of interest were isolated using a glass picking tool and cloning cylinders based on the colony morphology. After two steps of isolation, populations of LEC-like cells (LLCs) were generated and identified by the expression of lens marker genes by qPCR, western blot and immunofluorescence staining. The study introduced a modified protocol to isolate LLCs from iPSCs by defined factors in a short time frame. This technique could be useful for mechanistic studies of lens-related diseases. J. Cell. Physiol. 231: 2555-2562, 2016. 2016 Wiley Periodicals, Inc.

Ma F.,Fudan University | Ma F.,Key Laboratory of Myopia | Dai J.,Fudan University | Dai J.,Key Laboratory of Myopia | And 2 more authors.
Clinical and Experimental Ophthalmology | Year: 2014

Many clinical and fundamental studies have shown that high myopia (HM) and glaucoma are closely associated. In particular, the occurrence and progression of primary open-angle glaucoma interact with the progression of HM. Two hypotheses have been proposed to explain the association between the two disorders: the hypertension gene theory and the collagen-related gene theory. HM and primary open-angle glaucoma patients show similar collagen changes and hypersensitive responses to glucocorticoids. Consequently, these common features may hold key information regarding their underlying mechanisms. Advances in life sciences, such as molecular genetics, provide opportunities for clarifying their association at the molecular level. This article reviews available research on the association between these two disorders from the perspectives of epidemiology, clinical manifestation, diagnosis and pathogenic mechanisms. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Zhu X.-J.,Fudan University | Wolff D.,Key Laboratory of Myopia | Zhang K.-K.,Fudan University | He W.-W.,Fudan University | And 3 more authors.
Investigative Ophthalmology and Visual Science | Year: 2015

PURPOSE. The purpose of this study was to assess the inflammatory status of the aqueous humor in the fellow eye after uneventful cataract surgery in the first eye. METHODS. At the screening stage, aqueous humor samples from 15 first-eye and 15 second-eye cataract patients were collected just before cataract surgery and assayed using human cytokine antibody array. Screened cytokines were then verified using a suspension array system with aqueous humor samples obtained from 35 first-eye and 36 second-eye cataract patients. RESULTS. The cytokine antibody array revealed that interleukin-1 receptor antagonist (Il-1ra) and macrophage inflammatory protein (MIP)-1a and MIP-1b were expressed at high levels in first-eye patients and were lower in second-eye patients, whereas opposite trends were found for monocyte chemoattractant protein 1 (MCP-1) and for regulated on activation, normal T expressed and secreted (RANTES) (all, P < 0.05, Student’s t-test). However, only MCP-1 and IL-1ra were significantly different between the two groups after Bonferroni correction (both P < 0.00125). In the replication stage, the suspension cytokine array revealed that only MCP-1 expression was significantly greater in the aqueous humor of second-eye patients than in that of first-eye patients (P = 0.0067, Student’s t-test). CONCLUSIONS. This study revealed that expression of MCP-1, a pain-related inflammatory chemokine, was significantly increased in aqueous humor in the contralateral eye after firsteye cataract surgery. This suggests there may be a sympathetic ophthalmic type uveitis in the contralateral eye after first-eye cataract surgery and that may help to explain why second-eye phacoemulsification is often more painful. © 2015 The Association for Research in Vision and Ophthalmology, Inc.

Gao G.,Fudan University | Gao G.,Key Laboratory of Myopia | Dai J.,Fudan University | Dai J.,Key Laboratory of Myopia | And 4 more authors.
Clinical and Experimental Ophthalmology | Year: 2014

A meta-analysis was performed to evaluate the efficacy of methylprednisolone pulse therapy for Graves' ophthalmopathy. Eight studies involving 376 patients were included. A higher effective rate was found for patients treated with intravenous glucocorticoids (IVGC) over oral glucocorticoids (OGC) (risk ratio [RR]=1.48; 95% confidence interval [CI]=1.18-1.86). The combined IVGC and orbital radiotherapy (OR) was markedly more effective than OGC+OR (RR=1.40; 95% CI=1.11-1.77). IVGC resulted in an obvious reduction of clinical activity score (CAS) compared with OGC, with a weighted mean difference (WMD) of 0.86 (95% CI=0.53-1.18). The WMD for the reduction of the CAS between IVGC+OR and OGC+OR was 0.66 (95% CI=0.30-1.02). IVGC is an effective treatment and cause fewer adverse events. Limiting the total cumulative dose of methylprednisolone, careful patient selection and monitoring the condition of patients during treatment are necessary. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Zhou X.-Y.,Fudan University | Wang L.,Fudan University | Zhou X.-T.,Fudan University | Zhou X.-T.,Key Laboratory of Myopia | And 2 more authors.
Eye (Basingstoke) | Year: 2015

Purpose: The aim of this study was to investigate the wavefront aberration changes in human eyes caused by a gradient of increasing accommodation stimuli. Design: This is a prospective, single-site study. Methods: Healthy volunteers (n=22) aged 18-28 years whose refraction states were emmetropia or mild myopia, with astigmatism <1 diopter (D), were included in this study. After dilating the right pupil with 0.5% phenylephrine drops, the wavefront aberration of the right eye was measured continuously either without or with 1, 2, 3, 4, 5, or 6D accommodation stimuli (WFA1000B psychophysical aberrometer). The root mean square (RMS) values of the total wavefront aberrations, higher-order aberrations, and 35 individual Zernike aberrations under different accommodation stimuli were calculated and compared. Results: The average induced accommodations using 1, 2, 3, 4, 5, or 6D accommodation stimuli were 0.848, 1.626, 2.375, 3.249, 4.181, or 5.085 D, respectively. The RMS of total wavefront aberrations, as well as higher-order aberrations, showed no significant effects with 1-3 D accommodation stimuli, but increased significantly under 4, 5, and 6 D accommodation stimuli compared with relaxed accommodation. Zernike coefficients of Z0 4 significantly decreased with increasing levels of accommodation. Conclusion: Higher-order wavefront aberrations in human eyes changed with increased accommodation. These results are consistent with Schachar's accommodation theory. © 2015 Macmillan Publishers Limited.

Chen M.,Fudan University | Chen M.,Key Laboratory of Myopia | Dai J.,Fudan University | Dai J.,Key Laboratory of Myopia | And 4 more authors.
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2013

Background: To observe the efficacy and safety of modified Snyder-Thompson posterior scleral reinforcement in extensive high myopia of Chinese children. We had a retrospective design, and included a control group of children with natural progression of high myopia. Methods: This study included 64 eyes in 41 Chinese children with extensive high myopia who underwent modified Snyder-Thompson posterior scleral reinforcement surgery (PSR group), and 17 eyes in 11 age- and myopia-matched children who wore spectacles (control group). The mean follow-up was 4.99 ± 1.3 years in the PSR group and 4.48 ± 1.3 years in the control group. Axial length, spherical equivalent (SE), uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA) and fundus examinations were recorded before and after treatment, and complications were noted. Results: The mean change in SE at the end of the follow-up period was 1.5 ± 1.44 diopters (D) and 3.02 ± 1.57D in the PSR and control groups respectively. These changes were equivalent to an increase in axial length of 1.27 ± 0.54 mm and 2.05 ± 0.91 mm respectively. The PSR group showed less myopic progression and less eye elongation (p < 0.001). A notable increase in UCVA was only found in the PSR group (p = 0.0001). The improvement in BCVA was significantly greater in the PSR group (p = 0.0354). There were no serious complications of PSR surgery. Conclusion: The modified Snyder-Thompson PSR surgery was effective and safe in controlling extensive high myopia of Chinese children. © 2013 Springer-Verlag Berlin Heidelberg.

Li M.,Key Laboratory of Myopia | Zhou Z.,Yeshiva University | Shen Y.,Key Laboratory of Myopia | Knorz M.C.,Universitatsmedizin Mannheim | And 2 more authors.
Journal of Refractive Surgery | Year: 2014

PURPOSE: To compare the impact on corneal sensation after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (femto-LASIK) in patients with myopia. CopyrightMETHODS: In this prospective, nonrandomized comparative study, 71 subjects were enrolled. Thirty-eight eyes of 38 patients underwent SMILE and 33 eyes of 33 patients underwent femto-LASIK. Corneal sensation was tested with Cochet-Bonnet esthesiometry in five corneal areas preoperatively and at 1 week and 1, 3, and 6 months postoperatively. Comparison of corneal sensation was performed for the SMILE and femto-LASIK groups. Additionally, the correlations were evaluated between the postoperative corneal sensation, preoperative spherical equivalent, and ablation depth.RESULTS: All tested areas within the cap or flap demonstrated corneal hypoesthesia immediately after both surgeries. SMILE-treated eyes showed less compromised corneal sensation than femto-LASIK-treated eyes at all postoperative visits in the central, inferior, nasal, and temporal areas at the 1-week and 1-month visits. In the SMILE group, the inferior, nasal, and temporal quadrants recovered faster than other areas. In the femto-LASIK group, the sensation over the flap did not recover to preoperative levels by postoperative 6 months. There was no correlation between postoperative corneal sensation, preoperative spherical equivalent, and ablation depth in both groups.CONCLUSIONS: The impairment of corneal sensation was less significant in the SMILE group than in the femto-LASIK group and was independent of preoperative spherical equivalent or ablation depth. © SLACK Incorporated.

PubMed | University of Sydney and Key Laboratory of Myopia
Type: Journal Article | Journal: BMC ophthalmology | Year: 2016

To objectively compare the early changes in vault over time following implantation of an Implantable Collamer Lens without (ICL V4) and with (ICL V4c) a central hole and the respective factors affecting vault change in moderate to high myopia.This prospective study comprised of 38 eyes of 38 patients implanted with ICL V4 and 39 eyes of 39 patients implanted with ICL V4c intraocular lenses. We quantitatively assessed the postoperative values of vault and pupil size at 1day, 1week, and 1month following implantation using a rotating Scheimpflug camera (Pentacam). We compared these postoperative values within and between the two groups and identified the factors affecting vault change.The mean vaults at 1day, 1week, and 1month following ICL V4 implantation were 303.68185.11, 517.89160.07 and 521.32155.72m respectively, and those following ICL V4c were 316.67186.89, 495.13180.84 and 510.77175.51m, respectively. There was a significant difference in vault between 1day and 1week postoperatively. There was a significant association between the vault change and the pupil size change in both groups from 1day to 1month postoperatively (Pearman correlation coefficient; ICL V4: r=0.585, P=0.001; ICL V4c: r=0.588, P <0.001). The vault value 1month after implantation of ICL V4 and ICL V4c was associated with the preoperative anterior chamber depth, horizontal corneal diameter, horizontal and vertical sulcus-to-sulcus.Pupil movement is a critical factor in vault change, with increasing vault observed postoperatively from 1day to 1week associated with the declining effects of pharmacological miosis and increasing pupil size. The anterior chamber depth, horizontal corneal diameter, horizontal and vertical sulcus-to-sulcus show some correlation with vault.

Corneal biomechanical properties are always compromised after corneal refractive surgeries thus leading to underestimated intraocular pressure (IOP) that complicates the management of IOP. We investigated the changes in postoperative baseline of IOP values measured with noncontact tonometer (NCT), ocular response analyzer (ORA) and corvis scheimpflug technology (CST) in the early phase after small incision lenticule extraction (SMILE).Twenty-two eyes (-6.761.39D) of 22 moderate and high myopes, (28.367.14years, 12 male and 10 female) were involved in this prospective study. IOP values were measured using a non-contact tomometer (NCT-IOP), an ocular response analyzer (corneal-compensated IOP, IOPcc and Goldmann-correlated IOP, IOPg) and a Corvis scheimpflug technology tonometer (CST-IOP) preoperatively, at 20min and 24h, postoperatively. Repeated measures analysis of variance (RM-ANOVA), Pearsons correlation analysis and multiple linear regression models (stepwise) were performed. Cut-off P values were 0.05.Except for IOPcc, NCT-IOP, IOPg, and CST-IOP values significantly decreased after SMILE procedure (All P values <0.05). CCT, as well as MRSE and Km, did not significantly correlated with NCT-IOP, IOPcc, IOPg or CST-IOP, (all P values >0.05). Multiple linear regression models (stepwise) showed that the practical post-operative IOP value was the main predictor of the theoretical post-operative NCT-IOP, IOPcc and IOPg values (all P values <0.001). The postoperative applanation time 1 (AT1) value (B=8.079, t=4.866, P<0.001), preoperative central corneal thickness (CCT) value (B=0.035, t=2.732, P=0.014) and postoperative peak distance (PD) value (B=0.515, t=2.176, P=0.043) were the main predictors of the theoretical post-operative CST-IOP value.IOP values are underestimated when assessed after SMILE by using NCT-IOP, IOPg and CST-IOP. The practical postoperative IOPcc value and theoretical post-operative CST-IOP value may be more preferable for IOP assessment in the early phase after SMILE.Current Controlled Trials ChiCTRONRC13003114 . Retrospectively registered 17 March 2013.

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