Expression of Connective Tissue Growth Factor after Glaucoma Filtration Surgery in a Rabbit Model

Esson, Douglas W.; Neelakantan, Arvind; Iyer, Sandhya A.; Blalock, Timothy D.; Balasubramanian, Lakshmi; Grotendorst, Gary R.; Schultz, Gregory S.; Sherwood, Mark B.

doi:10.1167/iovs.03-0485

Cited by 54 publications

(48 citation statements)

References 39 publications

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“…The common clinical practice is to administer either 5-FU postoperatively by subconjunctival injection or MMC intraoperatively by local application. However, treatment with 5-FU and MMC is often associated with serious adverse effects, such as corneal epithelial defects, wound leaks, and hypotony with accompanying vision loss [1][2][3][4] . These problems have stimulated the search for alternative modes of drug delivery and new agents to minimize ocular complications.…”

Section: Discussionmentioning

confidence: 99%

“…The local use of antiproliferative agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), has improved the surgery outcome by preventing cell growth and scar formation. However, the administration of these drugs can result in a variety of toxicities, including wound leakage, corneal erosion and, rarely, necrosis of the corneal stroma and iris, chronic hypotony, corneal stromal neovascularization, and scleral ulceration [1][2][3][4] .…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus-mediated delivery of p27KIP1 to prevent wound healing after experimental glaucoma filtration surgery

et al. 2009

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Aim:The aim of the study was to evaluate the outcome of adenovirus-mediated p27 KIP1 (Ad-p27) expression on wound healing after filtration surgery and to investigate the inhibition of cell proliferation induced by Ad-p27. Methods: We constructed the adenovirus recombinant vector Ad-p27 and administered it to a rabbit model of glaucoma filtration surgery by subconjunctival injection; phosphate-buffered saline (PBS) and mitomycin C (MMC) were used as controls. Intraocular pressure (IOP), bleb scores, and anterior chamber depths were observed during a 28-d period. Histological examinations, fluorescence observations and Western blot analyses were evaluated. Results: Ad-p27 enhanced the surgical outcome and inhibited cell proliferation when compared with PBS. Bleb scores in the Ad-p27-treated eyes were higher than those in the PBS-treated eyes on d 7 (P<0.01), 14 (P<0.01) and 21 (P<0.05). On d 28, IOP remained significantly decreased in the Ad-p27 group compared with the PBS group (P<0.05). However, no differences in bleb scores or IOPs were observed between the Ad-p27 and MMC groups. Histological analysis showed that total cell numbers were markedly reduced, and less scar tissue was observed at the surgical site in eyes treated with Ad-p27. The number of fibroblasts was decreased in Tenon's capsule in Ad-p27-treated eyes; however, a marked and diffuse signal from the green fluorescent protein (GFP) was observed in fibroblasts. Western blot analysis revealed a high level of p27 KIP1 expression in conjunctival epithelium (P<0.01), relatively high expression in superficial scleral stroma (P<0.01), and low expression in corneal epithelium in the Ad-p27 group. Conclusions: Ad-p27 administration significantly improves the outcome of filtration surgery and inhibits postoperative proliferation in rabbit eyes. These findings suggest that p27 KIP1 is a potential adjunctive agent for inhibition of wound healing after filtration surgery.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated delivery of p27KIP1 to prevent wound healing after experimental glaucoma filtration surgery

et al. 2009

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“…To address this area of research, several animal models, including rat (10,11), rabbit (12)(13)(14)(15) and monkey (16,17), have been developed to study the clinical and histological scarring response after GFS. The rabbit has, by far, been the most popular animal used for such studies owing to both the relatively large ocular structures, allowing ease of surgical manipulation, and cost-effectiveness.…”

Section: Introductionmentioning

confidence: 99%

Validation of the Glaucoma Filtration Surgical Mouse Model for Antifibrotic Drug Evaluation

Seet

Lee

et al. 2011

Mol Med

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“…104 Given its profibrotic tendencies, it became a protein of interest in surgical models, demonstrating increased expression following glaucoma filtration surgery in rabbits and being associated with an elevated risk of bleb failure. 105,106 The putative role of CTGF in human glaucoma pathophysiology was first identified in pseudoexfoliation syndrome, 107,108 and attention soon focused on how CTGF regulates TM matrix deposition, 109,110 cellular tone, 111 and aqueous outflow facility. 112,113 In one promising recent study, the prostaglandin analog fluprostenol was found to mitigate CTGF-induced fibrogenesis in cultured human TM cells.…”

mentioning

confidence: 99%

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Chatterjee

Villarreal

Rhee

2014

Journal of Ocular Pharmacology and Therapeutics

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Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, and intraocular pressure (IOP) is an important modifiable risk factor. IOP is a function of aqueous humor production and aqueous humor outflow, and it is thought that prolonged IOP elevation leads to optic nerve damage over time. Within the trabecular meshwork (TM), the eye's primary drainage system for aqueous humor, matricellular proteins generally allow cells to modulate their attachments with and alter the characteristics of their surrounding extracellular matrix (ECM). It is now well established that ECM turnover in the TM affects outflow facility, and matricellular proteins are emerging as significant players in IOP regulation. The formalized study of matricellular proteins in TM has gained increased attention. Secreted protein acidic and rich in cysteine (SPARC), myocilin, connective tissue growth factor (CTGF), and thrombospondin-1 and -2 (TSP-1 and -2) have been localized to the TM, and a growing body of evidence suggests that these matricellular proteins play an important role in IOP regulation and possibly the pathophysiology of POAG. As evidence continues to emerge, these proteins are now seen as potential therapeutic targets. Further study is warranted to assess their utility in treating glaucoma in humans.

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Expression of Connective Tissue Growth Factor after Glaucoma Filtration Surgery in a Rabbit Model

Abstract: These data support the hypothesis that CTGF plays an important role in scarring and wound contracture after GFS. Inhibition of CTGF synthesis or its action may help prevent bleb failure and improve long-term GFS outcomes.

Cited by 54 publications

References 39 publications

Adenovirus-mediated delivery of p27KIP1 to prevent wound healing after experimental glaucoma filtration surgery

Adenovirus-mediated delivery of p27KIP1 to prevent wound healing after experimental glaucoma filtration surgery

Validation of the Glaucoma Filtration Surgical Mouse Model for Antifibrotic Drug Evaluation

Matricellular Proteins in the Trabecular Meshwork: Review and Update

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