Conditions for modifying intraocular lenses as drug carriers for methotrexate using poly (lactic-co-glycolic acid).

INTRODUCTION: The intraocular lens (IOL) can be used as a slow-release drug carrier in cataract surgery to alleviate posterior capsular opacification (PCO). The following is a systematic development of an IOL using methotrexate and the solvent casting process with poly (lactic-co-glycolic acid) (PLGA) as a carrier polymer. METHODS: Different solvents for PLGA and methotrexate were tested for dissolution properties and possible damage to the IOL. The required biological concentration of methotrexate was determined in human capsular bags implanted with an IOL. To detect fibrosis, α-SMA, f-actin, and fibronectin were labelled by immunofluorescence staining. Cell proliferation and extracellular matrix contraction were observed in a lens epithelial cell line (FHL-124). Finally, the IOL was designed, and an ocular pharmacokinetic model was used to measure drug release. RESULTS: Solvent mixtures were found to allow coating of the IOL with drug and PLGA without damaging it. PCO in the capsular bag model was inhibited above 1 µM methotrexate (p = 0.02). Proliferation in FHL-124 was significantly reduced above a concentration of 10 nM (p = 0.04) and matrix contraction at 100 nM (p = 0.02). The release profile showed a steady state within therapeutic range. CONCLUSION: After determination of the required physicochemical manufacturing conditions, a drug releasing IOL was designed. A favourable release profile in an ocular pharmacokinetics model could be shown.

Endogenous Galectin-1 Modulates Cell Biological Properties of Immortalized Retinal Pigment Epithelial Cells In Vitro.

In the eye, an increase in galectin-1 is associated with various chorioretinal diseases, in which retinal pigment epithelium (RPE) cells play a crucial role in disease development and progression. Since little is known about the function of endogenous galectin-1 in these cells, we developed a galectin-1-deficient immortalized RPE cell line (ARPE-19-LGALS1-/-) using a sgRNA/Cas9 all-in-one expression vector and investigated its cell biological properties. Galectin-1 deficiency was confirmed by Western blot analysis and immunocytochemistry. Cell viability and proliferation were significantly decreased in ARPE-19-LGALS1-/- cells when compared to wild-type controls. Further on, an increased attachment of galectin-1-deficient RPE cells was observed by cell adhesion assay when compared to control cells. The diminished viability and proliferation, as well as the enhanced adhesion of galectin-1-deficient ARPE-19 cells, could be blocked, at least in part, by the additional treatment with human recombinant galectin-1. In addition, a significantly reduced migration was detected in ARPE-19-LGALS1-/- cells. In comparison to control cells, galectin-1-deficient RPE cells had enhanced expression of sm-α-actin and N-cadherin, whereas expression of E-cadherin showed no significant alteration. Finally, a compensatory expression of galectin-8 mRNA was observed in ARPE-19-LGALS1-/- cells. In conclusion, in RPE cells, endogenous galectin-1 has crucial functions for various cell biological processes, including viability, proliferation, migration, adherence, and retaining the epithelial phenotype.

Pharmacological Therapy of Proliferative Vitreoretinopathy: Systematic In Vitro Comparison of 36 Pharmacological Agents.

Purpose: Proliferative vitreoretinopathy (PVR) is currently treated surgically. Reliable pharmaceutical options would be desirable, and numerous drugs have been proposed. This in vitro study is intended to systematically compare and determine the most promising candidates for the treatment of PVR. Methods: A structured literature review was conducted in the "PubMed" database to identify previously published agents proposed for medical treatment of PVR -36 substances that met the inclusion criteria. Toxicity and antiproliferative effects were evaluated on primary human retinal pigment epithelial (hRPE) using colorimetric viability assays. The seven substances with the widest therapeutic range between toxicity and no longer detectable antiproliferative effect were then validated with a bromodeoxyuridine assay and a scratch wound healing assay using primary cells derived from surgically excised human PVR membranes (hPVR). Results: Among 36 substances, 12 showed no effect on hRPE at all. Seventeen substances had a significant (P < 0.05) toxic effect of which nine did not have an antiproliferative effect. Fifteen substances significantly reduced hRPE proliferation (P < 0.05). The seven most promising drugs with the highest difference between toxicity and antiproliferative effects on hRPE were dasatinib, methotrexate, resveratrol, retinoic acid, simvastatin, tacrolimus, and tranilast. Whereof resveratrol, simvastatin, and tranilast additionally showed antiproliferative and dasatinib, resveratrol, and tranilast antimigratory effects on hPVR (P < 0.05). Conclusion: This study presents a systematic comparison of drugs that have been proposed for PVR treatment in a human disease model. Dasatinib, resveratrol, simvastatin, and tranilast seem to be promising and are well-characterized in human use.

Epiretinal Amniotic Membrane in Complicated Retinal Detachment: a Clinical and In Vitro Safety Assessment.

INTRODUCTION: Amniotic membrane (AM) is a popular treatment for external ocular diseases. First intraocular implantations in other diseases reported promising results. Here, we review three cases of intravitreal epiretinal human AM (iehAM) transplantation as an adjunct treatment for complicated retinal detachment and analyze clinical safety. Possible cellular rejection reactions against the explanted iehAM were evaluated and its influence was assessed on three retinal cell lines in vitro. METHODS: Three patients with complicated retinal detachment and implanted iehAM during pars plana vitrectomy are retrospectively presented. After removal of the iehAM at subsequent surgery, tissue-specific cellular responses were studied by light microscopy and immunohistochemical staining. We investigated the influence of AM in vitro on retinal pigment epithelial cells (ARPE-19), Müller cells (Mio-M1), and differentiated retinal neuroblasts (661W) . An anti-histone DNA ELISA for cell apoptosis, a BrdU ELISA for cell proliferation, a WST-1 assay for cell viability, and a live/dead assay for cell death were performed. RESULTS: Despite the severity of the retinal detachment, stable clinical outcomes were obtained in all three cases. Immunostaining of the explanted iehAM showed no evidence of cellular immunological rejection. In vitro, there was no statistical significant change in cell death or cell viability nor were proliferative effects detected on ARPE-19, Müller cells, and retinal neuroblasts exposed to AM. CONCLUSION: iehAM was a viable adjuvant with many potential benefits for treatment of complicated retinal detachment. Our investigations could not detect any signs of rejection reactions or toxicity. Further studies are needed to evaluate this potential in more detail.

A single intravenous injection of cyclosporin A-loaded lipid nanocapsules prevents retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a retinal disease that threatens the vision of prematurely born infants. Severe visual impairment up to complete blindness is caused by neovascularization and inflammation, progressively destroying the immature retina. ROP primarily affects newborns in middle- and low-income countries with limited access to current standard treatments such as intraocular drug injections and laser- or cryotherapy. To overcome these limitations, we developed a nanotherapeutic that effectively prevents ROP development with one simple intravenous injection. Its lipid nanocapsules transport the antiangiogenic and anti-inflammatory cyclosporin A efficiently into disease-driving retinal pigment epithelium cells. In a mouse model of ROP, a single intravenous injection of the nanotherapeutic prevented ROP and led to normal retinal development by counteracting neovascularization and inflammation. This nanotherapeutic approach has the potential to bring about a change of paradigm in ROP therapy and prevent millions of preterm born infants from developing ROP.

CCN2/CTGF-A Modulator of the Optic Nerve Head Astrocyte.

In primary open-angle glaucoma (POAG), a neurodegenerative disease of the optic nerve (ON) and leading cause of blindness, the optic nerve head (ONH) undergoes marked structural extracellular matrix (ECM) changes, which contribute to its permanent deformation and to degeneration of ON axons. The remodeling process of the ECM causes changes in the biomechanical properties of the ONH and the peripapillary sclera, which is accompanied by an increased reactivity of the resident astrocytes. The molecular factors involved in the remodeling process belong to the Transforming growth factor (TGF)-ß superfamily, especially TGF-ß2. In previous publications we showed that TGF-ß2 induced ECM alterations are mediated by Cellular Communication Network Factor (CCN)2/Connective Tissue Growth Factor (CTGF) and recently we showed that CCN2/CTGF is expressed by astrocytes of the ON under normal conditions. In this study we wanted to get a better understanding of the function of CCN2/CTGF under normal and pathologic conditions. To this end, we analyzed the glial lamina and peripapillary sclera of CCN2/CTGF overexpressing mice and studied the effect of CCN2/CTGF and increasing substratum stiffness on murine ON astrocytes in vitro. We observed enhanced astrocyte reactivity in the ONH, increased ECM protein synthesis in the peripapillary sclera and increased Ccn2/Ctgf expression in the ONH during the pathologic development in situ. CCN2/CTGF treatment of primary murine ON astrocytes induced a higher migration rate, and increase of ECM proteins including fibronectin, elastin and collagen type III. Furthermore, the astrocytes responded to stiffer substratum with increased glial fibrillary acidic protein, vimentin, actin and CCN2/CTGF synthesis. Finally, we observed the reinforced appearance of CCN2/CTGF in the lamina cribrosa of glaucomatous patients. We conclude that reactive changes in ONH astrocytes, induced by the altered biomechanical characteristics of the region, give rise to a self-amplifying process that includes increased TGF-ß2/CCN2/CTGF signaling and leads to the synthesis of ECM molecules and cytoskeleton proteins, a process that in turn augments the stiffness at the ONH. Such a scenario may finally result in a vicious circle in the pathogenesis of POAG. The transgenic CTGF-overexpressing mouse model might be an optimal model to study the chronic pathological POAG changes in the ONH.

Galectin-1 and -3 in high amounts inhibit angiogenic properties of human retinal microvascular endothelial cells in vitro.

PURPOSE: Galectin-1 and -3 are ß-galactoside binding lectins with varying effects on angiogenesis and apoptosis. Since in retinal pigment epithelial cells high amounts of human recombinant galectin (hr-GAL)1 and 3 inhibit cell adhesion, migration and proliferation, we investigated if hr-GAL1 and 3 have homologous effects on human retinal microvascular endothelial cells (HRMEC) in vitro. METHODS: To investigate the effect of galectin-1 and -3 on HRMEC, proliferation, apoptosis and viability were analyzed after incubation with 30, 60 and 120 µg/ml hr-GAL1 or 3 by BrdU-ELISA, histone-DNA complex ELISA, live/dead staining and the WST-1 assay, respectively. Further on, a cell adhesion as well as tube formation assay were performed on galectin-treated HRMEC. Migration was investigated by the scratch migration assay and time-lapse microscopy. In addition, immunohistochemical staining on HRMEC for ß-catenin, galectin-1 and -3 were performed and ß-catenin expression was investigated by western blot analysis. RESULTS: Incubation with hr-GAL1 or 3 lead to a decrease in proliferation, migration, adhesion and tube formation of HRMEC compared to the untreated controls. No toxic effects of hr-GAL1 and 3 on HRMEC were detected. Intriguingly, after treatment of HRMEC with hr-GAL1 or 3, an activation of the proangiogenic Wnt/ß-catenin signaling pathway was observed. However, incubation of HRMEC with hr-GAL1 or 3 drew intracellular galectin-1 and -3 out of the cells, respectively. CONCLUSION: Exogenously added hr-GAL1 or 3 inhibit angiogenic properties of HRMEC in vitro, an effect that might be mediated via a loss of intracellular endogenous galectins.

Anti-angiogenic properties of rapamycin on human retinal pericytes in an in vitro model of neovascular AMD via inhibition of the mTOR pathway.

PURPOSE: Choroidal neovascularizations (CNV) are partially stabilized through a coverage of pericytes leading to a partial anti-VEGF resistence. Drugs licensed for neovascular AMD (nAMD) do not take this mechanical and growth factor-driven CNV stability into account. The purpose of this work was to see if inhibiting the mammalian target of rapamycin (mTOR) may successfully block angiogenic cellular pathways in primary human retinal pericytes in an in vitro model of nAMD. METHODS: The mTOR inhibitor rapamycin was used to treat human retinal pericytes (HRP) at doses ranging from 0.005 to 15 g/ml. A modified metabolism-based XTT-Assay was used to assess toxicity and anti-proliferative effects. A scratch wound experiment showed the effects on migration. On Cultrex basement membrane gels, the influence of rapamycin on the development of endothelial cell capillary-like structures by human umbilical vein vascular endothelial cells (HUVEC) in the absence and presence of pericytes was investigated. RESULTS: Rapamycin showed no signs of toxicity within its range of solubility. The drug showed dose dependent anti-proliferative activity and inhibited migration into the scratch wound. Endothelial cell tube formation in a HUVEC monoculture was effectively inhibited at 45%. A co-culture of HUVEC with pericytes on Cultrex induced endothelial tube stabilization but was disrupted by the addition of rapamycin leading to degradation of 94% of the tubes. CONCLUSIONS: Rapamycin allows for an efficient modulation of aspects of angiogenesis in pericytes via mTOR-modulation in vitro. Further studies are needed to elucidate whether rapamycin may have an impact on CNV in nAMD in vivo.

Femtosecond laser-assisted descemetorhexis for Descemet membrane endothelial keratoplasty: cell-based and tissue-based ex vivo analysis of precision and safety.

PURPOSE: To analyze precision and safety of femtosecond laser-assisted descemetorhexis and postoperative corneal wound healing in human ex vivo specimens. SETTING: Department of Ophthalmology, University Hospital, LMU Munich, Munich, Germany. DESIGN: Experimental ex vivo study. METHODS: 4 donor corneas underwent femtosecond laser-assisted descemetorhexis. The descemetorhexis was performed using the LDV Z8 femtosecond laser, followed by live/dead staining, phase contrast microscopy, and scanning electron microscopy. The descemetorhexis parameters were set using a modified optical coherence tomography image capturing of 8 segments within a focus of 100 µm at the posterior corneal stroma (reversed capsulotomy program). RESULTS: Live/dead sample staining analysis demonstrated that the femtosecond laser had minimal impact on the vitality of surrounding endothelial cells. Phase contrast microscopy and scanning electron microscopy evaluation showed that the laser produced precise, clear-cut edges, leaving no stromal tissue bridges. CONCLUSIONS: Femtosecond laser-assisted descemetorhexis could serve as a safe and precise technique with only minimal endothelial cell damage. To minimize stromal damage, further laser energy profile adjustments are necessary to optimize corneal treatment within different stages of corneal tissue swelling.

Electron microscopy analysis of femtosecond laser-assisted capsulotomy before and after lens fragmentation.

Studying anterior lens capsule cutting edge profiles from femtosecond laser-assisted capsulotomy procedures performed before and after lens fragmentation. Twenty eyes (10 patients) with age-related cataract underwent femtosecond laser-assisted surgery (FLACS) using the Ziemer Z8 platform. First step of laser surgery was either capsulotomy (group first) or fragmentation (group second). One eye of each patient was assigned randomly, the second eye treated with the different sequence of procedures. After anterior capsule removal, tissue was fixed in cacodylate-buffered solution and cutting-edge profiles were analysed using scanning electron microscopy (SEM). All cases had cataract grade 2 and 3 based on LOCS III grading. SEM analysis showed more smooth edges in the first group, especially in cases with pseudoexfoliation (P = 0.037); more tags and bridges and a significant number of staggered cutting patterns (7 out of 10 cases) in the second group. All cases evolved the same microgroves with "valleys and mountains " as signs of the photodisruption process. Femtosecond laser capsulotomy should be performed before lens fragmentation minimizing the rate of cutting errors. Especially in eyes with advanced cataract, as intracapsular pressure may increase due to lens fragmentation without anterior capsular opening.

Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy.

In glaucoma therapy, nanoparticles (NPs) are a favorable tool for delivering drugs to the outflow tissues of the anterior chamber of the eye where disease development and progression take place. In this context, a prerequisite is an efficient enrichment of NPs in the trabecular meshwork with minimal accumulation in off-target tissues such as the cornea, lens, iris and ciliary body. We evaluated the optimal size for targeting the trabecular meshwork by using gold NPs of 5, 60, 80 and 120 nm with a bare surface (AuNPs) or coated with hyaluronic acid (HA-AuNPs). NPs were compared regarding their colloidal stability, distribution in the anterior chamber of the eye ex vivo and cellular uptake in vitro. HA-AuNPs demonstrated an exceptional colloidal stability. Even after application into porcine eyes ex vivo, the HA coating prevented an aggregation of NPs inside the trabecular meshwork. NPs with a diameter of 120 nm exhibited the highest volume-based accumulation in the trabecular meshwork. Off-target tissues in the anterior chamber demonstrated an exceptionally low gold content. Our findings are particularly important for NPs with encapsulated anti-glaucoma drugs because a higher particle volume would be accompanied by a higher drug payload.

Decorin-An Antagonist of TGF-ß in Astrocytes of the Optic Nerve.

During the pathogenesis of glaucoma, optic nerve (ON) axons become continuously damaged at the optic nerve head (ONH). This often is associated with reactive astrocytes and increased transforming growth factor (TGF-ß) 2 levels. In this study we tested the hypothesis if the presence or absence of decorin (DCN), a small leucine-rich proteoglycan and a natural inhibitor of several members of the TGF family, would affect the expression of the TGF-ßs and connective tissue growth factor (CTGF/CCN2) in human ONH astrocytes and murine ON astrocytes. We found that DCN is present in the mouse ON and is expressed by human ONH and murine ON astrocytes. DCN expression and synthesis was significantly reduced after 24 h treatment with 3 nM CTGF/CCN2, while treatment with 4 pM TGF-ß2 only reduced expression of DCN significantly. Conversely, DCN treatment significantly reduced the expression of TGF-ß1, TGF-ß2 and CTGF/CCN2 vis-a-vis untreated controls. Furthermore, DCN treatment significantly reduced expression of fibronectin (FN) and collagen IV (COL IV). Notably, combined treatment with DCN and triciribine, a small molecule inhibitor of protein kinase B (AKT), attenuated effects of DCN on CTGF/CCN2, TGF-ß1, and TGF-ß2 mRNA expression. We conclude (1) that DCN is an important regulator of TGF-ß and CTGF/CCN2 expression in astrocytes of the ON and ONH, (2) that DCN thereby regulates the expression of extracellular matrix (ECM) components and (3) that DCN executes its negative regulatory effects on TGF-ß and CTGF/CCN2 via the pAKT/AKT signaling pathway in ON astrocytes.

In vitro evaluation of simulated stereotactic radiotherapy for wet age-related macular degeneration on three different cell lines.

Low energy stereotactic radiotherapy has been proposed for the treatment of neovascular age related macular degeneration. We investigated the in vitro effect of the radiotherapy on pericytes, retinal pigment epithelium and endothelial cells. Primary human retinal pigment epithelium cells, human umbilical vein endothelial cells and human pericytes from Placenta were cultivated. In a pairwise protocol, one plate was irradiated at a dose of 16 Gy, while the second plate served as a non-irradiated control. Thereafter, cells were cultivated either in serum-free (non-permissive) or serum-stimulated (permissive) conditions. A life/dead assay, an XTT and a BrdU assay were performed up to 7 days after irradiation. No cell death occurred at any timepoint in any cell line after treatment nor in the control. Compared to the unirradiated controls, cell viability and metabolic activity were significantly reduced in irradiated cells in the XTT assay, except for non-permissive RPE cells. In the BrdU assay, proliferation was inhibited. While no cell death was detected in vitro, viability and proliferative capacity of all cell lines were significantly reduced. Therefore, it seems that low energy stereotactic radiotherapy inhibits angiogenesis without a direct induction of apoptosis but influencing microvascular function and stability.

A novel ocular function for decorin in the aqueous humor outflow.

Primary open-angle glaucoma, a neurodegenerative disorder characterized by degeneration of optic nerve axons, is a frequent cause of vision loss and blindness worldwide. Several randomized multicenter studies have identified intraocular pressure as the major risk factor for its development, caused by an increased outflow resistance to the aqueous humor within the trabecular meshwork. However, the molecular mechanism for increased outflow resistance in POAG has not been fully established. One of the proposed players is the pro-fibrotic transforming growth factor (TGF)-ß2, which is found in higher amounts in the aqueous humor of patients with POAG. In this study we elucidated the role of decorin, a small leucine-rich proteoglycan and known antagonist of TGF-ß, in the region of aqueous humor outflow tissue. Utilizing decorin deficient mice, we discovered that decorin modulated TGF-ß signaling in the canonical outflow pathways and the lack of decorin in vivo caused an increase in intraocular pressure. Additionally, the Dcn-/- mice showed significant loss of optic nerve axons and morphological changes in the glial lamina, typical features of glaucoma. Moreover, using human trabecular meshwork cells we discovered that soluble decorin attenuated TGF-ß2 mediated synthesis and expression of typical downstream target genes including CCN2/CTGF, FN and COL IV.  Finally, we found a negative reciprocal regulation of decorin and TGF-ß, with a dramatic downregulation of decorin in the canonical outflow pathways of patients with primary open-angle glaucoma. Collectively, our results indicate that decorin plays an important role in the pathogenesis of primary open-angle glaucoma and offers novel perspectives in the treatment of this serious disease.

The neuroprotective role of Wnt signaling in the retina.

The canonical Wnt/ß-catenin signaling pathway has been shown to play a major role during embryonic development and maturation of the central nervous system including the retina. It has a significant impact on retinal vessel formation and maturation, as well as on the establishment of synaptic structures and neuronal function in the central nervous system. Mutations in components of the Wnt/ß-catenin signaling cascade may lead to severe retinal diseases, while dysregulation of Wnt signaling can contribute to disease progression. Apart from the angiogenic role of Wnt/ß-catenin signaling, research in the last decades leads to the theory of a protective effect of Wnt/ß-catenin signaling on damaged neurons. In this review, we focus on the neuroprotective properties of the Wnt/ß-catenin pathway as well as its downstream signaling in the retina.

Posterior subcapsular cataracts are a late effect after acute exposure to 0.5 Gy ionizing radiation in mice.

PURPOSE: The long-term effect of low and moderate doses of ionizing radiation on the lens is still a matter of debate and needs to be evaluated in more detail. MATERIAL AND METHODS: We conducted a detailed histological analysis of eyes from B6C3F1 mice cohorts after acute gamma irradiation (60Co source; 0.063 Gy/min) at young adult age of 10 weeks with doses of 0.063, 0.125, and 0.5 Gy. Sham irradiated (0 Gy) mice were used as controls. To test for genetic susceptibility heterozygous Ercc2 mutant mice were used and compared to wild-type mice of the same strain background. Mice of both sexes were included in all cohorts. Eyes were collected 4 h, 12, 18 and 24 months after irradiation. For a better understanding of the underlying mechanisms, metabolomics analyses were performed in lenses and plasma samples of the same mouse cohorts at 4 and 12 h as well as 12, 18 and 24 months after irradiation. For this purpose, a targeted analysis was chosen. RESULTS: This analysis revealed histological changes particularly in the posterior part of the lens that rarely can be observed by using Scheimpflug imaging, as we reported previously. We detected a significant increase of posterior subcapsular cataracts (PSCs) 18 and 24 months after irradiation with 0.5 Gy (odds ratio 9.3; 95% confidence interval 2.1-41.3) independent of sex and genotype. Doses below 0.5 Gy (i.e. 0.063 and 0.125 Gy) did not significantly increase the frequency of PSCs at any time point. In lenses, we observed a clear effect of sex and aging but not of irradiation or genotype. While metabolomics analyses of plasma from the same mice showed only a sex effect. CONCLUSIONS: This article demonstrates a significant radiation-induced increase in the incidence of PSCs, which could not be identified using Scheimpflug imaging as the only diagnostic tool.

Development of a drug-eluting intraocular lens to deliver epidermal growth factor receptor inhibitor gefitinib for posterior capsule opacification prophylaxis.

PURPOSE: Different molecular targets, such as the epidermal growth factor receptor, have been identified for the prophylaxis of posterior capsule opacification. This led to the proposal of several drugs, yet drug delivery into the capsular bag remains challenging. The intraocular lens as a drug delivery device would provide a convenient method to allow drug release in the location needed. This is to evaluate the effect of a drug-eluting intraocular lens using an epidermal growth factor receptor inhibitor. METHODS: Hydrophobic and hydrophilic intraocular lenses were coated with gefitinib using the dip coating technique. The cellular response on the modified intraocular lenses was tested in a human lens epithelial cell line (FHL-124) in an anterior segment model. Furthermore, modified intraocular lenses were implanted into human capsular bags ex vivo. Drug release was determined as well as the biocompatibility on human corneal endothelial cells. Unmodified intraocular lenses served as controls. In addition, immunofluorescence staining with fibronectin as a marker for fibrotic response was conducted. RESULTS: Both coated hydrophilic and hydrophobic intraocular lenses could attenuate the cell growth of FHL-124 cells in the human capsular bag in comparison to the unmodified controls. Furthermore, gefitinib-soaked intraocular lenses showed a constant drug release over the first 10 days. No reduction in cell viability of corneal endothelial cells occurred. A decrease in fibronectin expression under gefitinib treatment could be observed. CONCLUSION: In vitro epidermal growth factor receptor seems to be a valuable target for the prevention of posterior capsule opacification. The gefitinib-eluting intraocular lens in this study could inhibit cell growth in non-toxic concentrations.