Davine Sijnave
Katholieke Universiteit Leuven
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Featured researches published by Davine Sijnave.
Investigative Ophthalmology & Visual Science | 2014
Sarah Van de Velde; Tine Van Bergen; Davine Sijnave; Karolien Hollanders; Karolien Castermans; Olivier Defert; Dirk Leysen; Evelien Vandewalle; Lieve Moons; Ingeborg Stalmans
PURPOSE To determine whether ROCK inhibition for the treatment of glaucoma can be improved by using novel, locally acting Rho kinase (ROCK) inhibitors, such as AMA0076, that lower IOP without inducing hyperemia. METHODS On-target potency of AMA0076 was compared with other ROCK inhibitors (Y-27632 and Y-39983) and conversion of AMA0076 into its functionally inactive metabolite was evaluated in rabbit eye tissues. Human trabecular meshwork (HTM) cell morphology, actin filaments, and focal adhesion were studied in vitro after exposure to AMA0076. The effect of AMA0076 on IOP was investigated in normotensive rabbits and a new, acute hypertensive rabbit model. Intraocular pressure lowering efficacy of AMA0076 was compared with pharmacologic treatments. Hyperemia after single topical dosing of AMA0076 and Y-39983 was scored. RESULTS AMA0076 and Y-39983 showed similar on-target potency. AMA0076 was most stable in aqueous humor and converted into its metabolite in other eye tissues. Exposure of HTM cells to AMA0076 led to significant and reversible changes in cell shape and a decrease in actin stress fibers and focal adhesions. Both AMA0076 and Y-39983 provided an equivalent IOP control. Compared with latanoprost and bimatoprost, AMA0076 was more potent in preventing the IOP elevation in the acute hypertensive rabbit model. The degree of hyperemia was significantly lower in rabbits treated with AMA0076 then with Y-39983. CONCLUSIONS AMA0076 is a locally acting ROCK inhibitor that is able to induce altered cellular behavior of HTM cells. Administration of AMA0076 effectively reduces IOP in ocular normotensive and acute hypertensive rabbits without causing distinct hyperemia.
Journal of Cellular and Molecular Medicine | 2013
Tine Van Bergen; Bart Jonckx; Karolien Hollanders; Davine Sijnave; Sarah Van de Velde; Evelien Vandewalle; Lieve Moons; Jean-Marie Stassen; Ingeborg Stalmans
Excessive post‐operative wound healing with subsequent scarring frequently leads to surgical failure of glaucoma filtration surgery (trabeculectomy). We investigated the hypothesis that placental growth factor (PlGF) plays a role in post‐operative scar formation, and that it therefore may be a target for improvement of filtration surgery outcome. ELISA experiments showed that PlGF levels were significantly increased in aqueous humour of glaucoma patients and after VEGF treatment, which may indicate an important contribution of this growth factor to wound healing after trabeculectomy. Using a mouse model of glaucoma filtration surgery, we were able to show that intracameral injection of a previously characterized anti‐PlGF antibody (ThromboGenics NV) significantly improved surgical outcome by increasing bleb survival and bleb area. This was associated with a significant reduction in post‐operative proliferation, inflammation and angiogenesis during the first post‐operative days after surgery, and with a decrease in collagen deposition at later stages. Furthermore, inhibition of PlGF seemed to be more effective than anti‐VEGF‐R2 treatment in improving surgical outcome, possibly via its additional effect on inflammation. These results render PlGF an appealing target for ocular wound healing and point to potential therapeutic benefits of PlGF inhibition for the prevention of surgical failure.
Cornea | 2015
Davine Sijnave; Tine Van Bergen; Karolien Castermans; Nele Kindt; Evelien Vandewalle; Jean-Marie Stassen; Lieve Moons; Ingeborg Stalmans
Purpose: To investigate the effect of AMA0526, a specific inhibitor of rho-associated protein kinase (ROCK), on corneal neovascularization (NV) and scarring in different in vitro and in vivo experimental models. Methods: The effect of AMA0526 on cell viability, proliferation, and migration of human umbilical vein endothelial cells was determined. Its in vivo topical effect on NV was investigated in the corneal micropocket mouse model (bevacizumab as a control). The vessel length, clock hours, and NV area were measured on photographs. The effect of AMA0526 on pathological wound healing was investigated in the alkali burn mouse model (dexamethasone as a control). Corneas were scored for corneal opacity (CO) and NV after burn injury. Immunohistochemistry was performed to study inflammation, blood vessel density, and collagen III deposition after 7 days. Results: ROCK inhibition significantly inhibited vascular endothelial cell proliferation and migration in vitro in a dose-dependent manner. In the micropocket model, NV was significantly reduced by AMA0526 (37% reduction, P < 0.05) comparable to bevacizumab. CO and NV were reduced after AMA0526, compared with the vehicle (P < 0.05 at all time points from day 3) after chemical burn. AMA0526 resulted in decreased inflammatory cell infiltration (26% reduction, P < 0.01), angiogenesis (47% reduction, P < 0.01), and collagen III deposition (27% reduction, P = 0.009) in the alkali burn model. AMA0526 administration showed results similar to those of dexamethasone with an additional antifibrotic effect. Conclusions: The ROCK inhibitor, AMA0526, efficiently inhibited angiogenesis in vitro, reduced CO and NV, and controlled the complete process of wound healing in vivo. These results warrant further investigation of the therapeutic potential of AMA0526 for corneal NV and scarring.
Investigative Ophthalmology & Visual Science | 2013
Karolien Hollanders; Tine Van Bergen; Davine Sijnave; Sarah Van de Velde; Evelien Vandewalle; Lieve Moons; Ingeborg Stalmans
Acta Ophthalmologica | 2013
S Van De Velde; T Van Bergen; Karolien Hollanders; Davine Sijnave; Evelien Vandewalle; Lieve Moons; Ingeborg Stalmans
Acta Ophthalmologica | 2012
S Van De Velde; T Van Bergen; Davine Sijnave; Karolien Hollanders; Lieve Moons; Ingeborg Stalmans
Acta Ophthalmologica | 2011
S Van De Velde; T Van Bergen; Evelien Vandewalle; Davine Sijnave; Karolien Hollanders; Dirk Leysen; Lieve Moons; Ingeborg Stalmans
Archive | 2014
Sarah Van de Velde; Tine Van Bergen; Evelien Vandewalle; Karolien Hollanders; Davine Sijnave; Lieve Moons; Ingeborg Stalmans
Investigative Ophthalmology & Visual Science | 2014
Davine Sijnave; Tine Van Bergen; Evelien Vandewalle; Karolien Castermans; Nele Kindt; Lieve Moons; Ingeborg Stalmans
Acta Ophthalmologica | 2014
Davine Sijnave; T Van Bergen; Evelien Vandewalle; Ingeborg Stalmans