Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes

By engaging CD36 on murine macrophages, thrombospondin-1 prevents excessive macrophage VEGF-C production and corneal neovascularization

Tolerability and safety of GS-101 eye drops, an antisense oligonucleotide to insulin receptor substrate-1: a ‘first in man’ Phase I investigation

AIMS: GS-101 (GeneSignal, Epalinges, Switzerland) is an antisense oligonucleotide that inhibits the expression of the scaffold protein insulin receptor substrate-1 (IRS-1). Inhibition of IRS-1 results in the prevention of neovascular growth and was shown to prevent the angiogenic process in preclinical in vitro and in vivo experiments. There is therefore a strong therapeutic rational for targeting angiogenesis in pathological neovascularization. We aimed to investigate the safety, tolerability and bioavailability of GS-101 eye drops. METHODS: This was a Phase I open-label study. The investigation was performed in two steps. Local ocular tolerability was first assessed with the application of one single low dose in one eye. After no signs of intolerance were observed in the subjects, the dose escalation phase of the study was initiated, and the remaining subjects received three times daily escalating doses of GS-101 in one eye for 14 days. RESULTS: The 14 healthy volunteers tolerated well 14 days' continued use of escalating doses of GS-101 from 43 to 430 microg per day. Other than itching, experienced also in the control eye by one subject and determined to be unrelated to the study treatment, no signs of intolerance were observed. CONCLUSIONS: The tolerability profile obtained from this study suggests that GS-101 is safe for human use. Further clinical evaluations in diseases related to abnormal angiogenesis are being targeted. In particular, the neovascularization-related orphan indications of corneal graft rejection, retinopathy of pre-maturity and neovascular glaucoma are currently under Phase II clinical investigation and are showing promising results

A Case of Ocular Benign Lymphoid Hyperplasia Treated with Bevacizumab Injection

We report the first case of ocular benign lymphoid hyperplasia (BLH) treated with subconjunctival injection of bevacizumab (Avastin). A 27-year-old man presented to our clinic with conjunctival masses and limbal neovascularization. An incisional biopsy yielded the diagnosis of BLH. The patient was subsequently given a subconjunctival injection of bevacizumab (1.25 mg / 0.1 mL). The patient did not experience recurrence or malignant metaplasia during the one-year follow-up period. In patients with conjunctival BLH, subconjunctival injection of bevacizumab can be a useful treatment option in patients unable to undergo a surgical procedure due to limbal neovascularization

Evaluation of a Novel Non-Diffractive Extended Depth of Focus Intraocular Lens : First Results from a Prospective Study

Purpose: To evaluate a novel hydrophobic, non-diffractive, extended depth of focus (EDOF) intraocular lens (IOL) design in comparison to two monofocal aspheric lenses. Methods: Inclusion criteria for this prospective, monocentric cohort study were opacification of the crystalline lens and patients’ wishes for surgery. In the case of the EDOF IOL, patients asked for a presbyopia correction. All patients received surgery on both eyes. Corrected and uncorrected distance visual acuity (CDVA, UCDVA), uncorrected and distance corrected intermediate visual acuity (UIVA, DCIVA) and defocus curves (all monocular and binocular) were compared three months postoperatively. Results: Fifty-six eyes were implanted with an EDOF IOL (LuxSmartTM, Bausch & Lomb GmbH, Berlin, Germany), 50 eyes with a monofocal aspheric IOL: 32 eyes with a clear IOL (PolylensVR AS 61, Polytech Domilens, Roßdorf, Germany), 16 eyes with a yellow IOL (iSertVR 251, Hoya Surgical Optics GmbH, Frankfurt, Germany). Three months postoperatively, UCDVA was comparable with the EDOF IOL, versus the monofocal IOL (P> 0.9). Binocular DCIVA in the EDOF IOL was significantly higher than in the monofocal IOL (P¼ 0.001). Monocular DCIVA better than 20/23 Snellen was achieved in 10% with the monofocal IOL and in 68% (P< 0.0001) with the EDOF IOL. Defocus curves showed a depth of focus at 20/23 Snellen of 1.6 vs. 0.83 diopters (D) in the EDOF IOL, vs. the monofocal IOL. No patient reported halos or starbursts in non-standardized questioning. Conclusion: This non-diffractive EDOF IOL provided comparably high UCDVA and significantly higher DCIVA than the mono-focal lenses, causing only mild optical phenomena

Dual Targeted Immunotherapy via In Vivo Delivery of Biohybrid RNAi-Peptide Nanoparticles to Tumor-Associated Macrophages and Cancer Cells

This work was funded in part by Science Foundation Ireland under Grant No. 11/PI/08, the National Key Basic Research Program (973 Project) (Nos. 2011CB933101 and 2015CB931802), National Natural Scientific Fund (Nos. 81225010 and 81327002), 863 project of China (Nos. 2012AA022703 and 2014AA020700), Shanghai Science and Technology Fund (No. 13NM1401500). E.R.E. was supported in part by NIH R01 GM49039. J.C. acknowledges Marie Curie International Outgoing Fellowship (FP7-PEOPLE-2013-IOF, Project No. 626386) and F.T. for Marie Curie grant agreement (PIEF-GA-2012-332-332462

Why Medical Students Are Crucial to the Future of Research in South Asia

One long-term strategy for promoting health research in developing countries is to target medical students early in their careers

UV light-blocking contact lenses protect against short-term UVB-induced limbal stem cell niche damage and inflammation

UVB irradiation has been linked to pathogenesis of pterygium, a conjunctival tumor growing onto transparent cornea, the windscreen of the eye. Due to corneal anatomy, ambient UVB irradiation is amplified at the stem cell-containing nasal limbus. The aim of this study was to analyse the effect of a UV-blocking contact lens (UVBCL, senofilcon A, Class 1 UV blocker) on limbal epithelial cells and fibroblasts under UVB irradiation compared to a non-UVB-blocking contact lens. UVBCL prevented UVB-induced DNA damage (as assessed by cyclobutane pyrimidine dimer immunostaining) as well as a decrease in proliferation and scratch wound closure rate of both limbal epithelial and fibroblast cells. Similarly, UVBCL protected limbal epithelial cells from UVB-induced loss of their phenotype in terms of colony forming efficiency and stem cell marker expression (ABCB5, P63α, integrin β1) compared to controls. Moreover, with UVBCL pro-inflammatory cytokines such as TNFα and MCP1 remained unchanged. These data demonstrate the significance of UV-protection in preserving the limbal niche in response to at least short-term UVB. Our data support the use of UVBCL in protecting limbal niche cells, especially after limbal stem cell transplantation and in patients after pterygium surgery, to help prevent recurrences

UV light-blocking contact lenses protect against short-term UVB-induced limbal stem cell niche damage and inflammation

UVB irradiation has been linked to pathogenesis of pterygium, a conjunctival tumor growing onto transparent cornea, the windscreen of the eye. Due to corneal anatomy, ambient UVB irradiation is amplified at the stem cell-containing nasal limbus. The aim of this study was to analyse the effect of a UV-blocking contact lens (UVBCL, senofilcon A, Class 1 UV blocker) on limbal epithelial cells and fibroblasts under UVB irradiation compared to a non-UVB-blocking contact lens. UVBCL prevented UVB-induced DNA damage (as assessed by cyclobutane pyrimidine dimer immunostaining) as well as a decrease in proliferation and scratch wound closure rate of both limbal epithelial and fibroblast cells. Similarly, UVBCL protected limbal epithelial cells from UVB-induced loss of their phenotype in terms of colony forming efficiency and stem cell marker expression (ABCB5, P63α, integrin β1) compared to controls. Moreover, with UVBCL pro-inflammatory cytokines such as TNFα and MCP1 remained unchanged. These data demonstrate the significance of UV-protection in preserving the limbal niche in response to at least short-term UVB. Our data support the use of UVBCL in protecting limbal niche cells, especially after limbal stem cell transplantation and in patients after pterygium surgery, to help prevent recurrences

Intravital Two-Photon Microscopy of Immune Cell Dynamics in Corneal Lymphatic Vessels

BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM). Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible physiological conditions