Safety and efficacy of intracapsular tranilast microspheres in experimental posterior capsule opacification

Wang, Man; Zhang, Jinjun; Jackson, Timothy L.; Sun, Jianguo; Wu, Wei; Marshall, John

doi:10.1016/j.jcrs.2007.07.041

Cited by 13 publications

(6 citation statements)

References 25 publications

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“…These include topical administration of anti-inflammation medications (e.g., dexamethasone, heparin, diclofenac) [6]–[8] or anti-metabolic agents (e.g., 5-fluorouracil, mitomycin) [9], [10], improved design of intraocular lens (IOL) [11], [12], new IOL materials, and modified surgical procedures (e.g., bag-in-the-lens IOL implantation, optic buttonholing) [13]–[15]. However, none of the pharmacological therapies is effective and safe enough for the prevention of PCO, and some of them are toxic [16], [17].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Pirfenidone on TGF-beta2 Induced Proliferation, Migration and Epithlial-Mesenchymal Transition of Human Lens Epithelial Cells Line SRA01/04

Yang

Lin

et al. 2013

PLoS ONE

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BackgroundPosterior capsular opacification (PCO) is a common complication of cataract surgery. Transforming growth factor-β2 (TGF-β2) plays important roles in the development of PCO. The existing pharmacological treatments are not satisfactory and can have toxic side effects.Methodologies/Principal FindingsWe evaluated the effect of pirfenidone on proliferation, migration and epithlial-mesenchymal transition of human lens epithelial cell line SRA01/04 (HLECs) in vitro. After treatment with 0, 0.25, and 0.5 mg/ml pirfenidone, cell proliferation was measured by MTT assay. Cell viability was determined by trypan blue exclusion assay and measurement of lactate dehydrogenase (LDH) activity released from the damaged cells. And cell migration was measured by scratch assay in the absence or presence of transforming growth factor-β2 (TGF-β2). The expressions of TGF-β2 and SMADs were evaluated with real-time RT-PCR, western blot, and immunofluorescence analyses. The mesenchymal phenotypic marker fibronectin (FN) was demonstrated by Immunocytofluorescence analyses. The cells had high viability, which did not vary across different concentrations of pirfenidone (0 [control] 0.3, 0.5 or 1.0 mg/ml) after 24 hours. Pirfenidone (0∼0.5 mg/ml) had no significant cytotoxicity effect on SRA01/04 by LDH assay. Pirfenidone significantly inhibited the proliferation and TGF-β2-induced cell migration and the effects were dose-dependent, and inhibited TGF-β2-induced fibroblastic phenotypes and TGF-β2-induced expression of FN in SRA01/04 cells. The cells showed dose-dependent decreases in mRNA and protein levels of TGF-β2 and SMADs. Pirfenidone also depressed the TGF-β2-induced expression of SMADs and blocked the nuclear translocation of SMADs in cells.ConclusionPirfenidone inhibits TGF-β2-induced proliferation, migration and epithlial-mesenchymal transition of human lens epithelial cells line SRA01/04 at nontoxic concentrations. This effect may be achieved by down regulation of TGF-β/SAMD signaling in SRA01/04 cells.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Pirfenidone on TGF-beta2 Induced Proliferation, Migration and Epithlial-Mesenchymal Transition of Human Lens Epithelial Cells Line SRA01/04

Yang

Lin

et al. 2013

PLoS ONE

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“…These include mitomycin-C,19 5-fluorouracil,20,21 and daunomycin 22. Recently, tranilast microspheres in a sustained-release formulation were used to inhibit and further reduce PCO in an animal model 23. The concept of using a system that allows sealed irrigation of the lens capsular bag and isolates the capsular bag from the remainder of the anterior segment permits targeting of LECs using pharmacological agents while minimizing the risk for damage to other intraocular structures.…”

Section: Discussionmentioning

confidence: 99%

Ablation of lens epithelial cells with a laser photolysis system: Histopathology, ultrastructure, and immunochemistry

Mamalis¹,

Grossniklaus²,

Waring³

et al. 2010

Journal of Cataract and Refractive Surgery

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PURPOSE-To evaluate efficacy of a neodymium:YAG (Nd:YAG) laser photolysis system in removing lens epithelial cells (LECs) and characterize the effect of the laser on laminin and fibronectin involved in LEC adhesion and migration.METHODS-Cadaver eyes were evaluated using the Miyake technique. The lenses were removed with phacoemulsification. The modified Nd:YAG laser was used to clean the LECs from the capsule. Only the fornix was cleaned in some eyes and the anterior subcapsular area in other eyes. Some areas were not treated and acted as controls. Standard irrigation/aspiration (I/A) removal of LECs was performed in additional eyes. The eyes were analyzed using light microscopy and immunohistochemical staining.RESULTS-Histopathologic evaluation showed that the laser removed the LECs from the anterior lens capsule and from the fornix. Immunohistochemical staining showed fibronectin and laminin staining in the untreated areas that was absent in the treated areas. Standard I/A removal of the LECs showed absence of cells but persistent laminin and fibronectin. Electron microscopy showed epithelial cells in untreated areas with an absence of the LECs and debris in treated areas. CONCLUSIONS-The laser photolysis system removed LECs from the anterior lens capsule and capsule fornix. Along with the cells, laminin, fibronectin, and cell debris remained in the untreated areas but were removed by the treatment. This treatment may be useful in preventing posterior capsule opacification.Financial Disclosure-No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.Cataract surgery with intraocular lens (IOL) implantation has evolved into a highly successful procedure; however, opacification of the capsular bag, including posterior capsule opacification (PCO), remains the most common complication of modern cataract surgery. The incidence of PCO ranges from 10% to 30% in the first several years after cataract surgery. In 1998, Schaumberg et al. 1 published a metaanalysis of the published literature on PCO; they found the postoperative incidence of PCO to be 11.8% at 1 year, 20.7% at 3 years, and 28.5% at 5 years.

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“…For these reasons, oral formulations of TL are used clinically to treat atopic dermatitis [23] and allergic asthma [24], and TL is used as an anti-allergic conjunctivitis allergy drug in the ophthalmic field [25]. In addition, TL attenuates the development of posterior subcapsular opacification after cataract surgery [26] and the onset and recurrence of pterygium [27]. Moreover, TL prevents corneal haze after photorefractive keratectomy [28,29], and reduces cell adhesions after strabismus surgery [30].…”

Section: Introductionmentioning

confidence: 99%

Development of Sustained-Release Ophthalmic Formulation Based on Tranilast Solid Nanoparticles

et al. 2020

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Eye drops containing Tranilast (TL), N-(3,4-dimethoxycinnamoyl) anthramilic acid, are used as an anti-allergic conjunctivitis drug in the ophthalmic field. Traditional eye drops are very patient compliant, although the bioavailability (BA) of most eye drops is low since eye drops cannot be instilled beyond the capacity of the conjunctival sac due to its limited volume. Thus, traditional eye drops have low BA and a short duration of the drug on the ocular surface, so solutions to these problems are highly anticipated. In this study, we designed a sustained-release drug-delivery system (DDS) for TL nanoparticles. TL nanoparticles were prepared by bead mill treatment, and the gel formulations containing TL nanoparticles (TL-NPs-Gel, particle size 50 nm–100 nm) were provided by carboxypolymethylene. The crystal structure of TL with and without bead mill treatment is the same, but the TL solubility in formulations containing nanoparticles was 5.3-fold higher compared with gel formulations containing TL microparticles (TL-MPs-Gel). The photo and thermal stabilities of TL-NPs-Gel are also higher than those of dissolved TL. Moreover, when TL-NPs-Gel is applied to the upper eyelid skin (outside), the TL is released as nanoparticles, and delivered to the lacrimal fluid through the meibomian glands. In addition, the TL release profile for TL-NPs-Gel was sustained over 180 min after the treatment. These findings can be used to develop a sustained-release DDS in the ophthalmic field.

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Safety and efficacy of intracapsular tranilast microspheres in experimental posterior capsule opacification

Abstract: Sustained-release intracapsular tranilast reduced PCO in an experimental model of PCO, suggesting further investigation of its therapeutic potential is justified.

Cited by 13 publications

References 25 publications

Inhibition of Pirfenidone on TGF-beta2 Induced Proliferation, Migration and Epithlial-Mesenchymal Transition of Human Lens Epithelial Cells Line SRA01/04

Inhibition of Pirfenidone on TGF-beta2 Induced Proliferation, Migration and Epithlial-Mesenchymal Transition of Human Lens Epithelial Cells Line SRA01/04

Ablation of lens epithelial cells with a laser photolysis system: Histopathology, ultrastructure, and immunochemistry

Development of Sustained-Release Ophthalmic Formulation Based on Tranilast Solid Nanoparticles

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