Polylactide-glycoli acid and rapamycin coating intraocular lens prevent posterior capsular opacification in rabbit eyes

Liu, Hongling; Wu, Lan; Fu, Shaoying; Hou, Yongzhong; Liu, Ping; Liu, Jingjing; Lin, Xichuan; Zhang, Xiaomei

doi:10.1007/s00417-008-1007-0

Cited by 32 publications

(29 citation statements)

References 29 publications

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“…Moreover, it has been verified that mTOR is activated during the TGF-β2-induced EMT in a time-dependent manner.Therefore, not only from the view of proliferation, but from EMT as well, rapamycin has the ability to control PCO [24]. An intraocular lens coating with polylactideglycoli acid and rapamycin effectively prevented formation and development of PCO for a relatively long duration in rabbit eyes [15,16]. The expression of pro-apoptotic protein Bax has often been associated with the increased apoptosis, while the anti-apoptotic protein Bcl-2 has been related with the inhibition of apoptosis in target cells [25,26,27].…”

Section: Resultsmentioning

confidence: 99%

“…Rapamycin, also known as Sirolimus, is a natural product isolated from Streptomyces hygroscopicus [12,13], a potent immunosuppressive drug which has been found to be able to inhibit proliferation of rabbit LECs in vitro [14] and promote the apoptosis in human LECs (HLECs) [15,16], and is currently used as an anti-tumor agent and an immunomodulatory medication, characterized with low toxicity and high efficiency [12,17,18,19,20,21,22,23]. Thus, rapamycin may be a potential inhibitor of PCO.…”

Section: Introductionmentioning

confidence: 99%

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Rapamycin-Induced Apoptosis in HGF-Stimulated Lens Epithelial Cells by AKT/mTOR, ERK and JAK2/STAT3 Pathways

Tian

Dong

Zhou

et al. 2014

IJMS

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Hepatocyte growth factor (HGF) induced the proliferation of lens epithelial cells (LECs) and may be a major cause of posterior capsule opacification (PCO), which is the most frequent postoperative complication of cataract surgery. To date, several agents that can block LECs proliferation have been studied, but none have been used in clinic. Recently, accumulating evidence has suggested rapamycin, the inhibitor of mTOR (mammalian target of Rapamycin), was associated with the induction of apoptosis in LECs. The purpose of our study was to investigate the potential effects of rapamycin on HGF-induced LECs and the underlying mechanisms by which rapamycin exerted its actions. Using cell proliferation, cell viability and flow cytometric apoptosis assays, we found that rapamycin potently not only suppressed proliferation but also induced the apoptosis of LECs in a dose-dependent manner under HGF administration. Further investigation of the underlying mechanism using siRNA transfection revealed that rapamycin could promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR, ERK and JAK2/STAT3 signaling molecules. Moreover, the forced expression of AKT, ERK and STAT3 could induce a significant suppression of apoptosis in these cells after treatment of rapamycin. Together, these findings suggested that rapamycin-induced apoptosis in HGF-stimulated LECs is accompanied by inhibition of AKT/mTOR, ERK and JAK2/STAT3 pathways, which supports its use to inhibit PCO in preclinical studies and provides theoretical foundation for future possible practice.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapamycin-Induced Apoptosis in HGF-Stimulated Lens Epithelial Cells by AKT/mTOR, ERK and JAK2/STAT3 Pathways

Tian

Dong

Zhou

et al. 2014

IJMS

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“…Additionally, the current data also indicate that a long-term constant drug concentration in the lens capsular bag seems necessary for the cytoskeletal drugs to effectively inhibit PCO. A possible method to meet this condition could be the implantation of a drug-coated IOL [49] after cataract surgery, since a controlled drug release from the coated IOL into the capsular bag might be maintained for 4 weeks or longer. Although the cell toxicity of the drugs may facilitate a permanent prevention of PCO, it also generates an ocular safety concern.…”

Section: Discussionmentioning

confidence: 99%

Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro

Sureshkumar¹,

Haripriya

Muthukkaruppan³

et al. 2011

Graefes Arch Clin Exp Ophthalmol

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Background To determine whether the cytoskeletal drugs H-7 and Latrunculin B (LAT-B) inhibit posterior capsular opacification (PCO) in the cultured human lens capsular bag. Methods Following extracapsular cataract (lens) extraction in human donor eyes, the capsular bag was prepared and cultured by standard techniques. Forty-eight capsular bags were studied, in which 13 were treated with H-7 (50, 100 or 300μM), 12 with 1% BSS (vehicle of H-7), 11 with LAT-B (2, 5 or 10μM), and 12 with 0.25% DMSO (vehicle of LAT-B). Forty out of the 48 capsular bags were from paired eyes of 20 donors with 1 bag being treated with H-7/LAT-B and the other with BSS/DMSO for each pair, including 20 for the H-7-BSS protocol and 20 for the LAT-B-DMSO protocol. The medium with the cytoskeletal drug/vehicle was replaced every 3–4 days for 4 weeks. PCO was assessed daily using inverted phase-contrast microscopy and scored on a 4-point scale. Results In all cultures with BSS or DMSO, residual lens epithelial cells (LECs) on the anterior capsule migrated to and proliferated on the posterior capsule by 3–7 days and apparent LEC growth on the posterior capsule with severe capsular wrinkling (PCO Grade 3) was seen by 2-3weeks. When treated continuously with H-7 or LAT-B, the migration and proliferation of LECs and the capsular wrinkling were inhibited in a dose-dependent manner, with the inhibition being complete (PCO Grade 0) in the 300μM H-7 (n=8, p<0.001) or 10μM LAT-B culture (n=3, p=0.002). Conclusion H-7 and LAT-B dose-dependently inhibited PCO formation in the cultured human lens capsular bags, suggesting that cytoskeletal drugs might prevent PCO formation after surgery in the human eye.

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“…The former method is simple, cost effective, and can be applied to either foldable or nonfoldable IOLs, but the drug release occurs over a short period of time [14,17]. The former method is simple, cost effective, and can be applied to either foldable or nonfoldable IOLs, but the drug release occurs over a short period of time [14,17].…”

Section: Drugs Loaded On and Released From Intraocular Lensesmentioning

confidence: 99%

“…These drugs include antibiotics [3 && ,4-10], corticosteroid [11][12][13], indomethacin [14,15], annexin [16] (to treat postcataract surgery inflammation) and various drugs, such as rapamycin [17], matrix metalloproteinases (MMPs) [18], selenocystamine [19], celecoxib [20], daunorubicin [21] and thapsigargin [22] [to inhibit posterior capsule opacification (PCO)]. These drugs include antibiotics [3 && ,4-10], corticosteroid [11][12][13], indomethacin [14,15], annexin [16] (to treat postcataract surgery inflammation) and various drugs, such as rapamycin [17], matrix metalloproteinases (MMPs) [18], selenocystamine [19], celecoxib [20], daunorubicin [21] and thapsigargin [22] [to inhibit posterior capsule opacification (PCO)].…”

Section: Introductionmentioning

confidence: 99%

Intraocular lens as a drug delivery reservoir

Liu

Wong

Mehta

2013

Current Opinion in Ophthalmology

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Polylactide-glycoli acid and rapamycin coating intraocular lens prevent posterior capsular opacification in rabbit eyes

Abstract: Our findings suggest that the designed RAPA-PLGA-IOL effectively prevented formation and development of PCO for a relatively long duration.

Cited by 32 publications

References 29 publications

Rapamycin-Induced Apoptosis in HGF-Stimulated Lens Epithelial Cells by AKT/mTOR, ERK and JAK2/STAT3 Pathways

Rapamycin-Induced Apoptosis in HGF-Stimulated Lens Epithelial Cells by AKT/mTOR, ERK and JAK2/STAT3 Pathways

Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro

Intraocular lens as a drug delivery reservoir

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