scholarly journals Integrin α5β1 Inhibition by CLT-28643 Reduces Postoperative Wound Healing in a Mouse Model of Glaucoma Filtration Surgery

2016 ◽  
Vol 57 (14) ◽  
pp. 6428 ◽  
Author(s):  
Tine Van Bergen ◽  
Grit Zahn ◽  
Patrizia Caldirola ◽  
Mario Fsadni ◽  
Ninus Caram-Lelham ◽  
...  
2016 ◽  
Vol 57 (7) ◽  
pp. 3381 ◽  
Author(s):  
Ajay Sharma ◽  
Govindaraj Anumanthan ◽  
Marcos Reyes ◽  
Huiyi Chen ◽  
Jacob W. Brubaker ◽  
...  

1998 ◽  
Vol 8 (1) ◽  
pp. 37-41 ◽  
Author(s):  
P.O. Denk ◽  
M. Knorr

The success of glaucoma filtration surgery depends mainly on an incomplete wound healing process in the area of the fistula. Since Kornblueth and Tenenbaum's investigations in 1956 it has been known that aqueous humour has intrinsic antiproliferative properties. It is assumed that ascorbic acid is involved in the regulation of the wound healing process after filtration surgery. To evaluate the antiproliferative effect of ascorbic acid in vitro, we used cultured fibroblasts of bovine Tenon's capsule and bovine sclera. Incubation of these cells with ascorbic acid at concentrations ranging from 0.5 to 3 mM/L led to dose-dependent inhibition of cell proliferation. The half-maximal inhibitory concentration was 1.0 mM/L for both cell types. Physiological concentrations of ascorbic acid may be valuable in the pharmacological prevention of failure of glaucoma filtration surgery. However, extensive clinical investigations are needed to clarify whether topical intraoperative or postoperative as well as oral administration of ascorbic acid inhibits fibroblast proliferation after glaucoma filtration surgery.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Keisuke Adachi ◽  
Yosuke Asada ◽  
Toshiaki Hirakata ◽  
Miki Onoue ◽  
Satoshi Iwamoto ◽  
...  

Abstract To clarify the early alterations of gene expression using a mouse model of glaucoma filtration surgery, we carried out microarray expression analysis. Using BALB/c mice, a filtration surgery model was made by incision of the limbal conjunctiva, followed by the insertion of a 33G needle tip into the anterior chamber, and 11-0 nylon sutures. Subgroups of mice were treated intraoperatively with 0.4 mg/ml mitomycin-C (MMC). At day 3 after surgery the bleb was maintained. The bleb region tissue was sampled 3 days after the filtration surgery, and gene expression analysis was carried out using a mouse Agilent 8 × 60 K array. We found 755 hyperexpressed transcripts in the bleb region compared to control conjunctiva. The hyperexpressed transcripts included epithelial cell metaplasia-related (Il1b, Krt16, Sprr1b), inflammation-related (Ccl2, Il6) and wound healing-related (Lox, Timp1) genes. We also found downregulation of a goblet cell marker gene (Gp2) in the bleb conjunctiva. MMC treatment suppressed elastin (Eln) gene expression and enhanced keratinization-related gene expression (Krt1, Lor) in the bleb region. Our results suggest the importance of epithelial wound healing after filtration surgery, and this filtration surgery model will be a useful tool for further pathophysiological analysis.


Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1126
Author(s):  
Manisha H. Shah ◽  
Elsa C. Chan ◽  
Nicole J. Van Bergen ◽  
Surinder S. Pandav ◽  
Sze Ng ◽  
...  

Collagen accumulation in sub-conjunctival tissue at the surgical wound is one of the major complications associated with glaucoma filtration surgery (GFS). This process often leads to unwanted fibrotic scar formation at the lesion site and dysfunction of tissues. Previously, we demonstrated that NADPH oxidase 4 (Nox4) is implicated in transforming growth factor-beta (TGFβ)-induced collagen production in ocular fibroblasts and scarring responses in a mouse model of corneal injury. Here, we propose that Nox4 is an important facilitator of TGFβ-induced responses. We tested this hypothesis in human Tenon’s fibroblasts (HTF) and also assessed a role of Nox4 in an experimental mouse model of GFS. TGFβ1 induced Nox4 mRNA expression but downregulated Nox5 in HTF. Targeting Nox4 gene expression with an adenovirus carrying a Nox4 small interfering RNA (siRNA) (Ad-Nox4i) or removal of hydrogen peroxide (H2O2) with EUK-134 (25 μM) in HTFs significantly reduced TGFβ1-induced Nox4 expression, H2O2 production, and collagen synthesis (p < 0.05, n = 3–6). SIS3 (5 μM) that prevents Smad3 phosphorylation is found to suppress TGFβ1-induced collagen production in HTFs. Furthermore, Ad-Nox4i and EUK-134 both abolished TGFβ1-stimulated proliferation of HTFs. We also compared collagen deposition at the wound arising from GFS between wildtype (WT) and Nox4 knockout (KO) mice. Both collagen deposition and fibrovascularization at the wound were significantly decreased in Nox4 KO mice at 14 days after GFS. Our results provide comprehensive evidence that Nox4 is an important mediator for TGFβ1-induced responses in HTFs and collagen deposition in surgical wound following GFS in mice. As such, pharmacological inhibition of Nox4 would be a viable therapeutic strategy for the control of scarring after glaucoma surgery.


2012 ◽  
Vol 90 ◽  
pp. 0-0
Author(s):  
D SIJNAVE ◽  
K HOLLANDERS ◽  
T VAN BERGEN ◽  
S VAN DE VELDE ◽  
E VANDEWALLE ◽  
...  

2005 ◽  
Vol 15 (5) ◽  
pp. 591-597 ◽  
Author(s):  
N. Akyol ◽  
S. Aydogan ◽  
N. Akpolat

Purpose To evaluate and compare the effectiveness of two adhesion barriers, Interceed and Seprafilm, on wound healing reaction after glaucoma filtration surgery. Materials and Methods Full-thickness filtration surgery was carried out on three groups, each containing four rabbits. Interceed and Seprafilm prepared in 3×4 mm dimensions was put on and around scleral opening in Groups 1 and 2, respectively. All groups received tobramycin and dexamethasone drops tid for 14 days. Intraocular pressure (IOP), anterior chamber depth, and bleb appearance were checked on the first, third, seventh, and 14th days. The rabbits were killed on the 14th day and the trabeculectomy area with overlying conjunctiva was excised. The samples were fixed with 10% formalin, buried in paraffin, and stained with hematoxylin and eosin. The surgical site and surrounding subconjunctival area were evaluated histopathologically for cell counts (fibroblast, lymphocyte, eosinophil, and macrophage), presence of edema and foreign body reaction, and potency of the fistula tract. Results Mean IOP at the first and third day examinations was significantly different between groups, but there was no statistically significant difference among the groups with respect to IOP, anterior chamber depth, or bleb appearance at the seventh and 14th days. The groups were similar with respect to number of fibroblasts, eosinophils, and neutrophils. Number of macrophages was significantly increased in Groups 1 and 2 and number of vessels was significantly decreased in Group 1. Conclusions Neither of these two adhesion-preventing substances seems to suppress wound healing reaction after glaucoma filtration surgery. However, a diminished wound healing reaction was expected with a decreased number of vessels, such as in Group 1. Increased number of macrophages in both groups may result in a decreased level of some inflammatory mediators.


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