Accumulation of latent transforming growth factor-β binding protein-1 and TGFβ1 in extracellular matrix of filtering bleb and of cultured human subconjunctival fibroblasts

Saika, Shizuya; Yamanaka, Osamu; Baba, Yukio; Kawashima, Yoshiji; Shirai, Kumi; Miyamoto, Takeshi; Okada, Yoshinori; Ohnishi, Yoshitaka; Ooshima, Akira

doi:10.1007/s004170100275

Cited by 43 publications

(26 citation statements)

References 15 publications

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“…However, the postoperative healing response can render the outcome of such surgery unsuccessful if scar formation increases outflow resistance of the artificially generated drainage pathway. The wound healing response at the operated site is characterized by several molecular events that include cell proliferation (particularly subconjunctival Tenon's capsule fibroblasts proliferation; Jampel et al, 1988), enhanced expression of ECM proteins (Saika et al, 2001) and inflammation (Chang et al, 2001b). Different approaches to modulate these processes during the wound healing response after filtering surgery by RNAi have been proposed.…”

Section: Fibrotic Eyementioning

confidence: 99%

Small‐interfering RNAs (siRNAs) as a promising tool for ocular therapy

Guzmán-Aránguez

Loma

Pintor

2013

British J Pharmacology

111

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RNA interference (RNAi) can be used to inhibit the expression of specific genes in vitro and in vivo, thereby providing an extremely useful tool for investigating gene function. Progress in the understanding of RNAi-based mechanisms has opened up new perspectives in therapeutics for the treatment of several diseases including ocular disorders. The eye is currently considered a good target for RNAi therapy mainly because it is a confined compartment and, therefore, enables local delivery of small-interfering RNAs (siRNAs) by topical instillation or direct injection. However, delivery strategies that protect the siRNAs from degradation and are suitable for long-term treatment would be help to improve the efficacy of RNAi-based therapies for ocular pathologies. siRNAs targeting critical molecules involved in the pathogenesis of glaucoma, retinitis pigmentosa and neovascular eye diseases (age-related macular degeneration, diabetic retinopathy and corneal neovascularization) have been tested in experimental animal models, and clinical trials have been conducted with some of them. This review provides an update on the progress of RNAi in ocular therapeutics, discussing the advantages and drawbacks of RNAi-based therapeutics compared to previous treatments. AbbreviationsAMD, age-related macular degeneration; Apaf-1, apoptotic protease-activating factor-1; CNV, choroidal neovascularization; CTGF, connective tissue growth factor; DR, diabetic retinopathy; dsRNA, double-stranded RNA; ECM, extracellular matrix; HIF-1α, hypoxia-inducible factor-1α; IOP, intraocular pressure; ONC, optic nerve crush; POAG, open-angle glaucoma; RGC, retinal ganglion cell; RISC, RNA-induced silencing complex; RNAi, RNA interference; RP, retinitis pigmentosa; Smad, signalling mathers against decapentaplegic; SPARC, secreted protein acidic and rich in cysteine; TLR3, toll-like receptor 3; TM, trabecular meshwork; TXNIP, thioredoxin interacting protein IntroductionRNA interference (RNAi) technology has been used to elucidate gene function, to generate model systems and to identify new molecular targets. In addition, RNAi is currently progressing from basic research to potential therapeutic applications. Because any gene that causes or contributes to a disease is susceptible to suppression by RNAi, RNAi therapy represents a promising biomedical strategy for treating a diverse range of diseases including cancer, cardiovascular diseases, neurodegenerative diseases, inflammatory conditions, viral infections and ocular diseases (Guo et al., 2010). In particular, the accessibility of the eye facilitates small-interfering RNA (siRNA) delivery, and naked siRNA has been efficiently applied by topical administration to the anterior segment or by intravitreal injection to the posterior segment (de Fougerolles, 2008). As the localized delivery of siRNA to the eye is less challenging than for other tissues, there has been significant progress made towards its use as a therapeutic procedure for eye diseases. In fact, several siRNA-based therapeutic agents for o...

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Section: Fibrotic Eyementioning

confidence: 99%

Small‐interfering RNAs (siRNAs) as a promising tool for ocular therapy

Guzmán-Aránguez

Loma

Pintor

2013

British J Pharmacology

111

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“…Among them, transforming growth factor β (TGFβ) is known to be the main growth factor involved in tissue fibrosis [3,4,36]. Smad family proteins have recently been reported to convey TGFβ signal between cell surface receptors and gene promoters, although other signaling cascades are also known [3,4].…”

Section: Introductionmentioning

confidence: 99%

Effects of interferon-γ on human subconjunctival fibroblasts in the presence of TGFβ1: reversal of TGFβ-stimulated collagen production

Yamanaka

Saika

Okada

et al. 2003

Graefe's Arch Clin Exp Ophthalmol

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“…Although tissue fibrosis is orchestrated by many growth factors/cytokines, transforming growth factor-␤ (TGF ␤ ) is believed to be one of the most important factors involved in tissue fibrosis including bleb fibrosis [1][2][3][4][5][6][7][8][9] . Clinical trials to reduce bleb fibrosis by topical administration of anti-TGF ␤ 2 neutralizing antibody reportedly resulted in a favorable result.…”

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confidence: 99%

Genipin Suppresses Subconjunctival Fibroblast Migration, Proliferation and Myofibroblast Transdifferentiation

Kitano

Saika²,

Yamanaka³

et al. 2006

Ophthalmic Res

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Purpose: Inchin-ko-to is a herbal medicine which has therapeutic effects in ameliorating liver fibrosis or cholestatic liver diseases. Its main bioactive component is genipin, which is an intestinal bacterial metabolite of this medication. Accordingly, we determined whether or not Inchin-ko-to suppresses in a wound healing model subconjunctival fibroblast (SCF) migration proliferation and myofibroblast transdifferentiation since an inhibitory effect could be of value in improving trabeculotomy outcome. Methods: Effects of genipin on SCF cell migration were examined subsequent to wounding confluent monolayer cultures. Alamar blue staining evaluated the effects of genipin (0–50 µg/ml) on fibroblast cell proliferation. Immunostaining determined α-smooth muscle actin (αSMA) expression. Western blotting evaluated (αSMA) expression and phospho-Smad2 formation. Real-time RT-PCR evaluated TGFβ1 and collagen Iα2 mRNA expression. Enzyme-immunoassay determined culture medium collagen I content. Results: Genipin suppressed wound-induced cell migration and proliferation. It also decreased collagen type I TGFβ1 and αSMA mRNA and protein expression. Smad2 signaling was inhibited by genipin in a dose-dependent manner. Conclusion: Genipin suppresses injury-induced fibrogenic responses in SCFs. This result suggests that the herbal medicine Inchin-ko-to might have therapeutic value following trabeculotomy.

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Accumulation of latent transforming growth factor-β binding protein-1 and TGFβ1 in extracellular matrix of filtering bleb and of cultured human subconjunctival fibroblasts

Cited by 43 publications

References 15 publications

Small‐interfering RNAs (siRNAs) as a promising tool for ocular therapy

Small‐interfering RNAs (siRNAs) as a promising tool for ocular therapy

Effects of interferon-γ on human subconjunctival fibroblasts in the presence of TGFβ1: reversal of TGFβ-stimulated collagen production

Genipin Suppresses Subconjunctival Fibroblast Migration, Proliferation and Myofibroblast Transdifferentiation

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