scholarly journals Pluripotent epigenetic regulator OBP-801 maintains filtering blebs in glaucoma filtration surgery model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuji Yamamoto ◽  
Atsushi Mukai ◽  
Toru Ikushima ◽  
Yasuo Urata ◽  
Shigeru Kinoshita ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rabbit Model ◽  
Vehicle Control ◽  
Control Group ◽  
Eye Drops ◽  
Subconjunctival Injection ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Vehicle Control Group ◽  
Epigenetic Regulator

AbstractInhibition of fibrosis is indispensable for maintaining filtering blebs after glaucoma filtration surgery (GFS). The purpose of this study was to investigate the ability of a pluripotent epigenetic regulator OBP-801 (OBP) to ameliorate extracellular matrix formation in a rabbit model of GFS. Rabbits that underwent GFS were treated with OBP. The gene expression profiles and intraocular pressure (IOP) were monitored until 30 postoperative days. The bleb tissues were evaluated for tissue fibrosis at 30 postoperative days. In in vitro models, OBP interfered the functions of diverse genes during the wound-healing process. In in vivo GFS models, the expressions of TGF-β3, MMP-2, TIMP-2 and 3, LOX, COL1A and SERPINH1 were significantly inhibited at 30 postoperative days in the OBP group compared with those in the vehicle control group. OBP treatment involving subconjunctival injection or eye drops showed no adverse effects, and reduced levels of α-SMA and collagen deposition at the surgical wound site. OBP maintained the long-lived bleb without scar formation, and IOP was lower at 30 postoperative days compared with the vehicle control group. These findings suggest that OBP is an effective and useful candidate low-molecular-weight agent for improving wound healing and surgical outcomes in a rabbit model of GFS.

scholarly journals The Effect of a Triple Combination of Bevacizumab, Sodium Hyaluronate and a Collagen Matrix Implant in a Trabeculectomy Animal Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 896
Author(s):  
Vanessa Andrés-Guerrero ◽  
Irene Camacho-Bosca ◽  
Liseth Salazar-Quiñones ◽  
Nestor Ventura-Abreu ◽  
Mercedes Molero-Senosiain ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Rabbit Model ◽  
Sodium Hyaluronate ◽  
Collagen Matrix ◽  
New Combination ◽  
Wound Healing Process ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Fibroblast Migration

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.

scholarly journals Effect of SMILE-derived decellularized lenticules as an adhesion barrier in a rabbit model of glaucoma filtration surgery

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Houfa Yin ◽  
Xinyi Chen ◽  
Xiaogang Hong ◽  
Jian Ma ◽  
Fang Wu ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Adjunctive Treatment ◽  
Control Group ◽  
Small Incision Lenticule Extraction ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Adhesion Barrier ◽  
Adverse Side Effects ◽  
Subconjunctival Space ◽  
Lenticule Extraction

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.

scholarly journals Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison with Mitomycin-C

2019 ◽  
Vol 21 (1) ◽  
pp. 63
Author(s):  
Emika Nemoto ◽  
Shota Kojima ◽  
Tetsuya Sugiyama ◽  
Denan Jin ◽  
Shinji Takai ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Kinase Inhibitor ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Eye Drops ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Significant Difference ◽  
Bleb Formation ◽  
Collagen Density

Regorafenib eye drops were developed for treating age-related macular degeneration. This study aimed to investigate the effects of this multi-kinase inhibitor on intraocular pressure (IOP), bleb formation, and conjunctival changes in a canine filtration surgery model. Glaucoma filtration surgery models were created in 24 eyes of 24 beagles. In experiment 1 (Ex 1), regorafenib eye drops (regorafenib group: n = 6) or a vehicle (control group, n = 6) were instilled twice daily for 4 weeks postoperatively. In experiment 2 (Ex 2), regorafenib eye drops were instilled as in Ex 1 (regorafenib group: n = 6) for 12 weeks while conventional intraoperative mitomycin-C (MMC) was utilized (MMC group: n = 6), In Ex 1, only the regorafenib group showed significant IOP reduction with a significantly higher bleb score. Subconjunctival area, collagen density, vessels, and cells showing proliferation and differentiation were lower in subconjunctival tissue in the regorafenib group. In Ex 2, no significant difference was found in IOP reduction and bleb formation between the regorafenib and MMC groups; bleb walls were significantly thicker and collagen density and vessels were higher in the regorafenib group; and no differences were observed in the above-mentioned cells. Thus, regorafenib might be a better alternative to MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery.

Effects Of SMILE-Derived Decellularized Lenticule As An Adhesion Barrier In A Rabbit Model of Glaucoma Filtration Surgery

2021 ◽  
Author(s):  
Houfa Yin ◽  
Xinyi Chen ◽  
Xiaogang Hong ◽  
Jian Ma ◽  
Fang Wu ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Adjunctive Treatment ◽  
Control Group ◽  
Small Incision Lenticule Extraction ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Adhesion Barrier ◽  
Adverse Side Effects ◽  
Subconjunctival Space ◽  
Lenticule Extraction

Abstract Background: To investigate the effects of small incision lenticule extraction (SMILE)-derived decellularized lenticule 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. Decellularized lenticule was placed in the subconjunctival space in one eye of the rabbits (decellularized lenticule group), and no adjunctive treatment was performed in the fellow eye (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 lenticule significantly increased bleb survival and decreased IOP postoperatively in the rabbit model with no adverse side effects. Histopathologic results showed a larger subconjunctival space and less subconjunctival fibrosis in the decellularized lenticule group. Conclusions: Decellularized lenticule can prevent postoperative conjunctiva-sclera adhesion and fibrosis, and it may represent a novel antifibrotic agent for trabeculectomy.

scholarly journals Epigenetic Modification Prevents Excessive Wound Healing and Scar Formation After Glaucoma Filtration Surgery

2016 ◽  
Vol 57 (7) ◽  
pp. 3381 ◽  
Author(s):  
Ajay Sharma ◽  
Govindaraj Anumanthan ◽  
Marcos Reyes ◽  
Huiyi Chen ◽  
Jacob W. Brubaker ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epigenetic Modification ◽  
Scar Formation ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery

scholarly journals Avoiding BAK in postoperative eye drops reduces the need for subconjunctival 5-FU injections post-trabeculectomy

2020 ◽  
Vol 17 (1) ◽  
pp. 128-131
Author(s):  
Keith Ong ◽  
Leonard Ong
Keyword(s):  
Intraocular Pressure ◽  
Mitomycin C ◽  
T Test ◽  
Topical Steroids ◽  
Eye Drops ◽  
Filtration Surgery ◽  
Glaucoma Filtration Surgery ◽  
Group A ◽  
Group B ◽  
Causes Of Failure

Purpose: Subconjunctival fibrosis is one of the main causes of failure of glaucoma filtration surgery. It can result in absence of a filtration bleb, a small scarred bleb, or a cystic bleb. 5-Fluorouracil (5-FU), mitomycin C (MMC), and topical steroids have been used to suppress subconjunctival fibrosis. Method: A study was done analyzing the number of postoperative subconjunctival 5-FU injections for trabeculectomy on pseudophakic eyes prior to and following the change to a BAK-free regimen. The cohort consisted of 16 consecutive cases undergoing primary trabeculectomy without intraoperative MMC or 5-FU. The trabeculectomy surgery included a groove sclerectomy procedure. Group A were 8 eyes of patients who had the author’s standard Chlorsig, Maxidex, and Prednefrin Forte eye drops tds. Group B were 8 eyes who had Chlorsig-dexamethasone and Optive-dexamethasone tds eye drops postoperatively. Results: Group B (BAK-free) patients required fewer postoperative 5-FU subconjunctival injections (average: 2.9, range: 1-5 injections) compared to Group A (BAK) patients (average: 7.3, range: 4-18 injections). This difference was statistically significant (P = 0.02, unpaired t-test). All patients had functioning blebs and did not require glaucoma medications to maintain target intraocular pressure. The Group B (BAK-free) patients had more diffuse blebs than the Group A (BAK) patients. Conclusion: The results demonstrated that when BAK was eliminated from postoperative eye drops in trabeculectomy, the number of postoperative 5-FU injections was reduced.

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