Overexpression of CDKN1B Inhibits Fibroblast Proliferation in a Rabbit Model of Experimental Glaucoma Filtration Surgery

2013 ◽  
Vol 54 (1) ◽  
pp. 343 ◽  
Author(s):  
Jian-gang Yang ◽  
Ying Deng ◽  
Ling-xiao Zhou ◽  
Xiao-yan Li ◽  
Peng-rui Sun ◽  
...  
PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0138054 ◽  
Author(s):  
Gina M. Martorana ◽  
Jamie L. Schaefer ◽  
Monica A. Levine ◽  
Zachary L. Lukowski ◽  
Jeff Min ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 896
Author(s):  
Vanessa Andrés-Guerrero ◽  
Irene Camacho-Bosca ◽  
Liseth Salazar-Quiñones ◽  
Nestor Ventura-Abreu ◽  
Mercedes Molero-Senosiain ◽  
...  

Currently available anti-scarring treatments for glaucoma filtration surgery (GFS) have potentially blinding complications, so there is a need for alternative and safer agents. The effects of the intrableb administration of a new combination of the anti-VEGF bevacizumab, sodium hyaluronate and a collagen matrix implant were investigated in a rabbit model of GFS, with the purpose of modulating inflammation, angiogenesis, fibroblast migration and fibrogenesis in the wound healing process. A comparative-effectiveness study was performed with twenty-four rabbits, randomly assigned to the following treatments: (a) biodegradable collagen matrix implant (Olo), (b) bevacizumab-loaded collagen matrix implant (Olo-BVZ), (c) bevacizumab-loaded collagen matrix implant combined with sodium hyaluronate (Olo-BVZ-H5) and (d) sham-operated animals (control). Rabbits underwent a conventional trabeculectomy and were studied over 30 days in terms of intraocular pressure and bleb characterization (height, area and vascularity in central, peripheral and non-bleb zones). Histologic differences among groups were further evaluated at day 30 (inflammation, total cellularity and degree of fibrosis in the area of surgery). Local delivery of bevacizumab (Olo-BVZ and Olo-BVZ-H5) increased the survival of the filtering bleb by 21% and 31%, respectively, and generated a significant decrease in inflammation and cell infiltration histologically 30 days after surgery, without exhibiting any local toxic effects. Olo-BVZ-H5 showed less lymphocyte infiltration and inflammation than the rest of the treatments. Intraoperative intrableb implantation of bevacizumab, sodium hyaluronate and a collagen matrix may provide an improved trabeculectomy outcome in this model of intense wound healing. This study showed an effective procedure with few surgical complications and a novel combination of active compounds that offer new possibilities to improve the efficacy of filtration surgery.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yong Yao Chun ◽  
Zhu Li Yap ◽  
Li Fong Seet ◽  
Hiok Hong Chan ◽  
Li Zhen Toh ◽  
...  

AbstractSmall interfering RNA (siRNA) therapy is a promising epigenetic silencing strategy. However, its widespread adoption has been severely impeded by its ineffective delivery into the cellular environment. Here, a biocompatible injectable gelatin-based hydrogel with positive-charge tuned surface charge is presented as an effective platform for siRNA protection and delivery. We demonstrate a two-step synthesis of a gelatin-tyramine (Gtn-Tyr) hydrogel with simultaneous charge tunability and crosslinking ability. We discuss how different physiochemical properties of the hydrogel interact with siSPARC (siRNA for secreted protein, acidic and rich in cysteine), and study the positive-charge tuned gelatin hydrogel as an effective delivery platform for siSPARC in anti-fibrotic treatment. Through in vitro studies using mouse tenon fibroblasts, the positive-charge tuned Gtn-Tyr hydrogel shows sustained siSPARC cellular internalization and effective SPARC silencing with excellent biocompatibility. Similarly, the same hydrogel platform delivering siSPARC in an in vivo assessment employing a rabbit model shows an effective reduction in subconjunctival scarring in post glaucoma filtration surgery, and is non-cytotoxic compared to a commonly used anti-scarring agent, mitomycin-C. Overall, the current siRNA delivery strategy involving the positive-charge tuned gelatin hydrogel shows effective delivery of gene silencing siSPARC for anti-fibrotic treatment. The current charge tunable hydrogel delivery system is simple to fabricate and highly scalable. We believe this delivery platform has strong translational potential for effective siRNA delivery and epigenetic silencing therapy.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Houfa Yin ◽  
Xinyi Chen ◽  
Xiaogang Hong ◽  
Jian Ma ◽  
Fang Wu ◽  
...  

Abstract Background To investigate the effects of small incision lenticule extraction (SMILE)-derived decellularized lenticules on intraocular pressure (IOP) and conjunctival scarring in a rabbit model of glaucoma filtration surgery. Methods Trabeculectomy was performed on both eyes of New Zealand rabbits. A decellularized lenticule was placed in the subconjunctival space in one eye of the rabbits (the decellularized lenticule group), and no adjunctive treatment was performed in the fellow eye (the control group). The filtering bleb features and IOP were evaluated 0, 3, 7, 14, 21, and 28 days after surgery, and histopathologic examination was performed 28 days after surgery. Results Decellularized lenticules significantly increased bleb survival and decreased IOP postoperatively in the rabbit model with no adverse side effects. The histopathologic results showed a larger subconjunctival space and less subconjunctival fibrosis in the decellularized lenticule group. Conclusions Decellularized lenticules can prevent postoperative conjunctiva-sclera adhesion and fibrosis, and they may represent a novel antifibrotic agent for trabeculectomy.


2005 ◽  
Vol 46 (1) ◽  
pp. 191 ◽  
Author(s):  
Salvatore Grisanti ◽  
Peter Szurman ◽  
Max Warga ◽  
Radoslaw Kaczmarek ◽  
Focke Ziemssen ◽  
...  

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