Incidence and risk factors for ocular GVHD after allogeneic hematopoietic stem cell transplantation.

We analyzed the incidence and risk factors for ocular GVHD in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Korea. In this retrospective, noncomparative, observational study, 635 subjects were included who had at least 2 years of follow-up ophthalmological examinations after allo-HSCT from 2009 to 2012 at Seoul St Mary's Hospital, Seoul, Korea. The mean duration between allo-HSCT and onset of ocular GVHD was 225.5±194.3 days. The adjusted incidence for acute ocular GVHD was 1.33% and that for chronic GVHD was 33.33%. In the multivariate analysis, preexisting diabetes mellitus (odds ratio (OR): 4.22, 95% confidence interval (CI): 1.66-10.72), repeated allo-HSCT (OR: 29.10, 95% CI: 1.02-8.28) and the number of organs that chronically developed GVHD by stage I (OR: 14.63, 95% CI: 9.81-21.84) increased risk of ocular GVHD. Careful monitoring of ocular GVHD is needed in patients with chronic GVHD in multiple organs and preexisting diabetes.

TGF-ß1 regulates cell fate during epithelial-mesenchymal transition by upregulating survivin.

Members of the transforming growth factor beta (TGF-ß) superfamily are multifunctional cytokines that regulate several cellular processes, including cell cycle arrest, differentiation, morphogenesis, and apoptosis. TGF-ß promotes extracellular matrix production and morphological change. Morphogenetic responses to TGF-ß include cell migration and epithelial-mesenchymal transition (EMT), which are critical during embryogenesis, development of fibrotic diseases, and the spreading of advanced carcinomas. The purpose of this study was to clarify how TGF-ß regulates the fate of retinal pigment epithelial (RPE) cells. TGF-ß1 promoted cell cycle progression and phosphorylation of retinoblastoma protein (Rb) in ARPE-19 cells. TGF-ß1 induced survivin expression, which in turn stabilized tubulin and Aurora B. RT-PCR and western blot analysis revealed that survivin expression increased in ARPE-19 cells following TGF-ß1 treatment. When survivin was depleted, TGF-ß1 induced cell cycle arrest and apoptosis and also reduced Rb phosphorylation. In conclusion, the present study shows that induction of EMT in human RPE cells upregulates survivin, leading to survivin-dependent inhibition of cell cycle arrest and apoptosis. Whether cells undergo EMT or apoptosis in response to TGF-ß1 is dependent on their cell cycle state, and TGF-ß1 regulates the cell cycle via survivin.

Toll-like receptor 4 signalling attenuates experimental allergic conjunctivitis.

Allergic conjunctivitis from an allergen-driven T helper type 2 (Th2) response is characterized by conjunctival eosinophilic infiltration. Association between signalling through Toll-like receptor 4 (TLR-4) and adaptive immune responses has been observed in allergic airway disease. We examined whether administration of bacterial lipopolysaccharide (LPS), a prototypic bacterial product that activates immune cells via TLR-4, could affect the development of allergic conjunctivitis and modify the immune response to ovalbumin (OVA) allergen in an experimental allergic conjunctivitis (EAC) model. Mice were challenged with two doses of OVA via conjunctival sac after systemic challenge with OVA in alum. Several indicators for allergy were evaluated in wild-type and TLR-4(-/-) mice with or without adding of different doses of LPS into OVA in alum. Mice challenged with OVA via conjunctival sac following systemic challenge with OVA in alum had severe allergic conjunctivitis. Of interest, LPS administration markedly suppressed immunoglobulin (Ig)E-mediated and eosinophil-dependent conjunctival inflammation. In addition, mice sensitized with OVA plus LPS had less interleukin (IL)-4, IL-5 and eotaxin secretion than mice sensitized with OVA only. The suppression of allergic response by LPS administration was due to Th1 shift. In contrast, the presence of LPS during sensitization with OVA had no effect on severity of allergic conjunctivitis and Th2 responses in TLR4-4(-/-) mice. Our findings demonstrate, for the first time, that LPS suppresses Th2 responses via the TLR-4-dependent pathway in the EAC model.

Evaluating the effects of granular and membrane filtrations on chlorine demand in drinking water.

In this study, chlorine decay experiments were conducted for the raw water from Nakdong River that is treated by Chilseo Water Treatment Plant (CWTP) situated in Haman, Korea as well as the effluents from sand and granular activated carbon (GAC) filters of CWTP and fitted using a chlorine decay model. The model estimated the fast and slow reacting nitrogenous as well as organic/inorganic compounds that were present in the water. It was found that the chlorine demand due to fast and slow reacting (FRA and SRA) organic/inorganic substances was not reduced significantly by sand as well as GAC filters. However, the treated effluents from those filters contained FRA and SRA that are less reactive and had small reaction rate constants. For the effluents from microfiltration, ultrafiltration, and nanofiltration the chlorine demand because FRA and SRA were further reduced but the reaction rate constants were larger compared to those of sand and GAC filter effluents. This has implications in the formation of disinfection by products (DBPs). If DBPs are assumed to form due to the interactions between chlorine and SRA, then it is possible that the DBP formation potential in the effluents from membrane filtrations could be higher than that in the effluents from granular media filters.

Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients.

PURPOSE: To investigate the possibility of collagen type VIII alpha2 (COL8A2) as a potential susceptibility gene for Korean patients with Fuchs' corneal dystrophy (FECD), we performed mutation screening of the COL8A2 gene. METHODS: A total of 25 FECD patients were screened, including 15 patients from six pedigrees with early onset FECD and an additional 10 unrelated patients, all of Korean ancestry. Seventy-three control individuals without corneal disease were selected from the general population. PCR-SSCP and direct sequencing were used to screen genetic variations in COL8A2. The pathogenic impact of these sequence variants was evaluated through the SIFT and PolyPhen algorithms. RESULTS: We have identified a novel heterozygous mutation, Q455V, in exon 2 of COL8A2. All patients of Korean pedigrees with FECD had the Q455V mutation, and two out of nine unrelated cases also had this mutation. But it was not present in unaffected individuals from these pedigrees or from control groups. Two heterozygous missense mutations, R155Q and T502M, were also observed, but, they showed no significant difference between FECD patients and controls. The allele frequencies of A35A and G495G, which were synonymous substitutions, were significantly associated with FECD. Both Q455V and T502M were predicted as deleterious mutations by computational methods using PolyPhen and SIFT. CONCLUSIONS: Our data constitute the first report of a heterozygous Q455V mutation of the COL8A2 gene in Korean patients with FECD. Q455V may be the causative defect in the development and progression of Korean FECD patients.

Association of -31T>C and -511 C>T polymorphisms in the interleukin 1 beta (IL1B) promoter in Korean keratoconus patients.

PURPOSE: To investigate the genetic association between unrelated Korean keratoconus patients and interleukin 1 alpha (IL1A), interleukin 1 beta (IL1B), and IL1 receptor antagonist (IL1RN) gene polymorphisms. METHODS: We investigated the association between IL1A (rs1800587, rs2071376, and rs17561), IL1B (rs1143627, rs16944, rs1143634, and rs1143633), and IL1RN (rs419598, rs423904, rs424078, and rs315952, variable number tandem repeat [VNTR]) polymorphisms in 100 unrelated Korean keratoconus patients. One hundred control individuals without any corneal disease were selected from the general population. Polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) analysis and direct sequencing were used to screen for genetic variations in the IL1 gene cluster. Haplotypes for the IL1 gene cluster were constructed using Haploview version 4.0. RESULTS: We analyzed a total of 12 polymorphic sites in the IL1 gene cluster. Among them, the -511 (rs16944) and -31 (rs1143627) positions in the promoter region of IL1B were significantly different between patient and control groups. The C allele of rs16944 (-511C>T, p=0.022, odds ratio of risk [OR]=1.46, 95% confidence intervals [CI] 0.94<2.27) and the T allele of rs1143627 (-31T>C, p=0.025, OR=1.43, 95% CI 0.92<2.22) were associated with a significantly increased risk of keratoconus in Korean patients. Linkage of the two alleles, -31*C and -511*T, was associated with an increased risk for keratoconus with OR=2.38 (p=0.012, 95% CI=1.116-5.046). The *C/*A genotype of rs2071376 in IL1A intron 6 was significantly different between the keratoconus patients and control subjects (p=0.034, OR=0.59, 95% CI 0.32<1.11). Other polymorphisms did not show an association with keratoconus risk. CONCLUSIONS: This is the first report of IL1 gene cluster mutation screening in Korean keratoconus patients. Significant differences in allelic frequency of IL1B between keratoconus patients and the control group suggest that IL1B polymorphisms may play a role in the susceptibility of unrelated Koreans to develop keratoconus.

Comparison of clinical results between heparin surface modified hydrophilic acrylic and hydrophobic acrylic intraocular lens.

PURPOSE: To compare the clinical results of heparin surface modified (HSM) hydrophilic acrylic intraocular lens (IOL) with those of hydrophobic acrylic IOL. METHODS: One hundred patients with cataract were randomized to receive one of acrylic foldable IOLs after phacoemulsification: HSM hydrophilic acrylic IOL (n=50) BioVue3 (BioVue, OII, Ontario, CA, USA) and hydrophobic acrylic IOL (n=50) Sensar (AR40e, AMO, Santa Ana, CA, USA). Bestcorrected visual acuity and refractive error were measured at 1 week, 2 months, 6 months and 12 months after surgery in both IOL groups. To assess posterior capsular opacification (PCO), digital retroillumination image of posterior capsule was analyzed at 12 months using POCOman software. RESULTS: Best-corrected visual acuity (log MAR) was 0.032+/-0.082 in BioVue3 group and 0.034+/-0.077 in Sensar group at 12 months. There was no statistically significant difference between the two groups (p=0.554). Refractive error was -0.247+/-0.821 diopter in BioVue3 group and -0.264+/-0.808 diopter in Sensar group at 12 months. There was no statistically significant difference of refractive error between the two groups (p=0.909). At 12 months, BioVue3 IOL group had a lower percentage area and severity of PCO than Sensar group. However, it was not statistically significant (p=0.349, p=0.288). No Nd:YAG capsulotomy was performed in BioVue3 group while it was required in two eyes (4.0%) in Sensar group. CONCLUSIONS: There was no statistically significant difference of postoperative visual acuity, refractive error and degree of PCO between HSM hydrophilic acrylic IOL and hydrophobic acrylic IOL.

Ligand release-independent transactivation of epidermal growth factor receptor by transforming growth factor-beta involves multiple signaling pathways.

Many of the signaling responses induced by transforming growth factor-beta (TGF-beta) are mediated by Smad proteins, but there is evidence that it can also signal independently of Smads. Here, we provide evidence that multiple signal pathways induced by TGF-beta1-including Src family tyrosine kinases (SFKs), generation of reactive oxygen species (ROS), de novo protein synthesis and E-cadherin-dependent cell-cell interactions-transactivate the epidermal growth factor receptor (EGFR), which in turn regulates expression of c-Fos and c-Jun. Immunoprecipitation and immunofluorescence staining showed that EGFR was phosphorylated on tyrosine in response to TGF-beta1. EGFR transactivation required the activation of SFKs and the production of ROS via NADPH oxidase, but was not dependent on metalloproteases or the release of EGF-like ligands. In addition, the production of ROS was dependent on signaling by specific SFKs as well as de novo protein synthesis. Stable transfection of E-cadherin into MDA-MB-231 cells as well as E-cadherin-blocking assays revealed that E-cadherin-mediated cell-cell interactions were also essential for EGFR transactivation. Finally, EGFR transactivation was involved in the expression of c-Fos and c-Jun via the extracellular signal-regulated kinase signaling cascade. Taken together our data suggest that ligand release-independent transactivation of EGFR may diversify early TGF-beta signaling and represent a novel pathway leading to TGF-beta-mediated gene expression.

The expression of multiple cytokines and inducible nitric oxide synthase in experimental melanin-protein-induced uveitis.

We investigated the kinetics of multiple cytokines and inducible nitric oxide synthase (iNOS) in experimental uveitis induced by bovine melanin protein (BMP) for the proper treatment of uveitis. Experimental uveitis was induced in male Lewis rats by injection of BMP. The levels of various inflammatory cytokines and iNOS mRNAs were semiquantified by the reverse-transcriptase reaction followed by PCR. The uveitis was started to develop at approximately day 14 and peaked around 21 days after immunization. The signs of uveitis disappeared by 4 weeks after immunization. When the inflammation was severest, TNF-alpha, IL-1alpha, IL-10, IFN-gamma and iNOS mRNA increased to their peak, which varied with the degree of induction and different time course. We concluded that both cytokines and iNOS might modulate the inflammation at different states of experimental melanin-protein-induced uveitis. Their combination will be necessary for an effective treatment of inflammation.

Attenuation of Zn2+ neurotoxicity by aspirin: role of N-type Ca2+ channel and the carboxyl acid group.

Synaptically released Zn2+ ions enter into neurons primarily through voltage-gated Ca2+ channels (VGCC) or N-methyl-d-aspartate (NMDA) receptors, which can mediate pathological neuronal death. We studied the possibility (and underlying mechanisms) that aspirin, known to prevent NMDA neurotoxicity, would also attenuate Zn2+ neurotoxicity. Administration of 3 to 10 mM aspirin, in cortical cell cultures, attenuated the evolution of neuronal death following exposure to 300 microM Zn2+ for 30 min. This neuroprotective effect of aspirin was attributable to the prevention of Zn2+ ion entry. Aspirin interfered with inward currents and an increase in [Ca2+]i through VGCC and selective binding of omega-conotoxin, sensitive to N-type Ca2+ channel. The omega-conotoxins GVIA or MVIIC, the selective inhibitors of N-type Ca2+ channels, attenuated Zn2+ neurotoxicity. Aspirin derivatives lacking the carboxyl acid group did not reduce Zn2+ neurotoxicity. The present findings suggest that aspirin prevents Zn2+-mediated neuronal death by interfering with VGCC, and its action specifically requires the carboxyl acid group.

BIGH3 gene mutations and rapid detection in Korean patients with corneal dystrophy.

PURPOSE: Mutations in the BIGH3 gene on chromosome 5q31 cause four distinct autosomal dominant corneal dystrophies. We sought to determine whether the BIGH3 gene mutation was responsible for corneal dystrophy in Korean patients. METHODS: Polymerase chain reaction single strand conformational polymorphism (PCR-SSCP) analysis was performed with the DNA from patients and healthy individuals. We sequenced the PCR products with the aberrant SSCP pattern to identify the mutation. Mutant-specific reverse primers were used to screen genomic DNA for the identified mutations. RESULTS: We identified mutations R124C in the CDL1 family and R124H in four families with a granular dystrophy. We identified our granular dystrophy to be Avellino corneal dystrophy (ACD). Eighteen of 20 patients with a granular dystrophy contained the same R124H mutation, indicating that mutation R124H was very common in Korean patients with ACD. During this study, we identified a new polymorphism (T1667C, F540F). CONCLUSIONS: This is the first report of mutations found in the BIGH3 gene in Korean families with corneal dystrophy. We report that the majority (90%) of ACD patients in Korea carry the R124H mutation. Mutant-specific reverse primers can be used to screen efficiently for CDL1 and ACD.

Expression of vascular endothelial growth factor and inducible nitric oxide synthase in pterygia.

PURPOSE: To evaluate the expression of vascular endothelial growth factor (VEGF) in pterygium and investigate the interrelationships between VEGF and nitric oxide (NO) in the development of pterygia. METHODS: Specimens of normal conjunctiva acquired incidentally to conjunctival transplantation during pterygium and strabismus surgery and the excised pterygium were used in this study. Cryopreserved tissue specimens consisting of normal conjunctiva and pterygium were used to study the expression of VEGF and inducible NO synthetase (iNOS), using immunohistochemistry. For confirmation of NOS activity, reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was done. Enzyme-linked immunosorbent assay (ELISA) for detection and quantification of VEGF was performed. RESULTS: Expression of VEGF and iNOS was strongly revealed mainly in the epithelium of the head portions of pterygial specimens, although not in the epithelium of conjunctival ones. Pterygial epithelium was stained with NADPH diaphorase, confirming NOS activity. ELISA showed a greater amount of VEGF in pterygium (11.7 +/- 2.1 pg/mg) compared with normal conjunctiva (4 +/- 0.47 pg/mg) ( p < 0.05). CONCLUSION: These data are the first to demonstrate that VEGF and NO may play an important role in the development of pterygium and to identify VEGF and NO in the epithelium of pterygium. We hypothesize that environmental stress, such as ultraviolet irradiation and local inflammation stimulate the elaboration of NO and VEGF, resulting in the conjunctival fibrovascular ingrowth characteristic of pterygium.

Predictability for proper capsular tension ring size and intraocular lens size.

Predicting correct capsular tension ring size and intraocular lens size using measurements of lens diameter, corneal diameter, axial length and capsular bag diameters to determine anatomical relationships of post implantation capsular tension ring (CTR). The vertical and horizontal diameters of cornea and lens were measured in 62 human eyeballs supplied from the eye bank of the Catholic University. The relationship between corneal diameter and axial length was examined in 195 living human eyes. An extension of capsular bag diameter after implantation of CTR was measured in 19 pigs' eyes purchased from a slaughter house. The correlation between the lens diameter and the capsular bag diameter after CTR implantation was analyzed using linear regression. The average diameters (mean of horizontal and vertical diameters) of cornea and lens in human eyeball of postmortems (average age:69, ratio of male:female = 23:39) were 11.59+/-0.42 mm for horizontal diameter, 9.54+/-0.27 mm, for vertical diameter. The average corneal diameters and axial lengths in living human eyes (average age: 62, ration of male:female = 84:111) were 11.63+/-0.53 mm for the cornea diameter, 24.48+/-2.10 mm, for cornea axial length. There is a statistically significant correlation between corneal diameter and axial length (correlation coefficient=0.788; p<0.001) and corneal diameter and lens diameter (correlation coefficient=0.711; p<0.001). In pigs' eyes, there is a relationship between lens diameter and capsular bag diameter after implantation of 11 mm CTR (correlation coefficient=0.684; p<0.001). In conclusion, axial length and corneal diameter may give surgeons a valuable clue to expected size of capsular bag and important parameters for selecting the correct sized CTR and IOL.

Central islands after LASIK detected by corneal topography.

A central island is defined as a localized elevated area in corneal topography after excimer laser application for myopic correction. We experienced 15 cases of central islands developed 1 week after LASIK using VISX STAR on corneal topography. The uncorrected visual acuity and best corrected visual acuity were 0.52 +/- 0.22, 0.66 +/- 0.25 in central islands group and 0.69 +/- 0.19, 0.78 +/- 0.19 in control group at 1 week after LASIK. The visual acuity in control group was more improved statistically significantly than central islands group (respectively p = 0.01, p = 0.03). There was no statistical significance between the two groups, although the uncorrected visual acuity and best corrected visual acuity were somewhat more increased in control group at 2 months and 6 months after LASIK than in central islands group (respectively p = 0.06, p = 0.24 at 2 months, p = 0.10, p = 0.17 at 6 months). On the changes of spherical equivalent after LASIK, both the central islands group and control group were in hyperopic state at 1 week after LASIK and were somewhat regressed to myopia at 2 months and 6 months after LASIK. But there was no statistical significance between the two groups at different time points (respectively p = 0.15, p = 0.64, p = 0.67). In 12 cases the central islands were disappeared spontaneously at 2 months, but in 3 cases the central islands were remained 6 months after LASIK on corneal topography. In the one case of 3 cases the best corrected visual acuity was 0.5 at 6 months after LASIK, but in the others the best corrected visual acuity was not different from the mean best corrected visual acuity. Most cases in LASIK, the central islands were dissapeared without specific treatments as in PRK. We suggest, in the case of central islands at 6 months after LASIK, that if the patient complain visual discomfort, monocular diplopia, haloes, or ghost images, central reablation with excimer laser should be considered.

Complestatin is a noncompetitive peptide antagonist of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors: secure blockade of ischemic neuronal death.

Complestatin, a peptide derived from Streptomyces, was found to protect cultured cortical neurons from excitotoxicity induced by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or kainate. This neuroprotective behavior of complestatin was attributed to a blockade of Ca2+ ion entry and accumulation, after the activation of NMDA and AMPA/kainate receptors. Complestatin reversibly interfered with NMDA- and AMPA-mediated excitatory synaptic transmission. Complestatin also protected cortical neurons from prolonged deprivation of oxygen and glucose, more effectively than combined antagonists of NMDA and AMPA/kainate receptors. Neurotoxicity, evolving within 1 to 2 days after continuous exposure to combined NMDA and AMPA/kainate antagonists, was not observed in cortical cell cultures that were exposed to complestatin. Finally, complestatin dose dependently prevented neuronal death evolving within the inner nuclear and ganglion cell layers, after transient retinal ischemia. We conclude that complestatin possesses novel pharmacological properties that effectively prevent excitotoxicity under certain pathological conditions.

Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells.

Transforming growth factor-beta (TGF-beta) is known to be a causative factor in pathological fibrosis and the metastasis of cancer cells, through effects on molecules of the extracellular matrix (ECM). We evaluated the influence of TGF-beta(1) on the gene expression of matrix metalloproteinase-2 (MMP-2) in lens epithelial cells (LECs). The results showed that TGF-beta(1) induced the expression of mRNA for MMP-2 in LECs. Subsequently, in order to examine the role of MMP-2, we overexpressed MMP-2 in LECs by stable transfection. The MMP-2-overexpressing LECs showed typical indicators of a myofibroblast-like cell phenotype, such as multiple layers of cells, elongated morphology, and expression of alpha-smooth muscle actin. We also showed that an MMP inhibitor blocked the TGF-beta(1)-induced morphological change in LECs. These results demonstrate that MMP-2 plays a role in the transformation of LECs, which has implications for the pathological fibrosis of these cells.

Hydrogen peroxide is a novel inducer of connective tissue growth factor.

Connective tissue growth factor (CTGF) has recently been described as a fibrogenic factor and is greatly induced by various extracellular stimuli, such as transforming growth factor-beta (TGF-beta), dexamethasone, and serotonin. CTGF induces collagen type I and fibronectin, and the deposition of such molecules leads to fibrotic disease in many tissues. Intracellular reactive oxygen species (ROS) are generated by extracellular stress conditions and are produced as by-products of cellular metabolism. Imbalanced cellular redox status is a potent pathogenic factor that leads to various degenerative diseases, including tissue fibrosis. Since CTGF is believed to play a crucial role in fibrotic disease formation in many tissues, we examined the role of ROS in CTGF gene expression in human lens epithelial cell line B3. The results showed that CTGF was induced by reactive oxygen species such as hydrogen peroxide and hydroxyl radicals. Next, we examined whether CTGF induction by ROS is via newly synthesized TGF-beta. The results showed that ROS directly induced CTGF mRNA not via the increased TGF-beta synthesis or activation. Next, we treated AG490, which is the well-known inhibitor of Janus kinase (JAK), with hydrogen peroxide. AG490 abrogated the CTGF induction by ROS in a dose-dependent manner. The results suggest that JAK-2/-3 seems to be involved in the enhanced CTGF mRNA expression by hydrogen peroxide. In this report, we present that hydrogen peroxide is a novel inducer of CTGF gene expression and that JAK-2/-3 activation seems to play a role in CTGF induction.

Downregulated expression of integrin alpha6 by transforming growth factor-beta(1) on lens epithelial cells in vitro.

Integrins represent the main cell surface receptors that mediate cell-matrix and cell-cell interactions. They play critical roles in adhesion, migration, morphogenesis, and the differentiation of several cell types. Previous studies have demonstrated that members of the fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-beta(1), and insulin growth factor (IGF)-1 play important roles in lens biology. In particularly, TGF-beta(1) appears to play a key role in extracellular matrix production, cell proliferation, and cell differentiation of lens epithelial cells. In this study we investigated the effects of FGF-2, TGF-beta(1), and IGF-1 on the modulation of integrin receptors using lens epithelial cell lines (HLE B-3 and alphaTN-4) and lens explants. We found that the expression of integrin alpha6 is downregulated by TGF-beta(1), but is not responsive to FGF-2 or IGF-1. The promoter activity of the integrin alpha6 gene decreased upon TGF-beta(1) treatment in a transient transfection assay, and flow cytometric analysis demonstrated the reduced expression of integrin alpha6 by TGF-beta(1), whereas significant changes were not observed in the level of integrin alpha6 after the addition of FGF-2. These findings suggest that the reduced expression of integrin alpha6 caused by TGF-beta(1) might play a role in the activation of the cell cycle genes required during the fiber differentiation of the lens.

Effect of a capsular tension ring on the shape of the capsular bag and opening and the intraocular lens.

PURPOSE: To evaluate the effect of a capsular tension ring (CTR) on the shape of the capsular bag, the extent of the capsular opening, and the shape of intraocular lenses (IOLs). SETTING: Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea. METHODS: The corneal button was removed from porcine eyes in vitro. After phacoemulsification was performed, an IOL alone or an IOL and CTR were inserted in the capsular bag in 6 groups of 5 eyes each. The eyes were examined from the posterior aspect using a Miyake technique to assess capsular bag shape and the capsular opening. To evaluate effects of the CTR on IOL shape, rabbit eyes had phacoemulsification and IOL implantation with and without placement of a CTR in vivo. The IOLs were removed from enucleated eyes 3 months postoperatively and compared with unused control IOLs. RESULTS: The differences between the maximum and minimum diameters of the capsular bags and capsular openings were significantly less in groups with a CTR. Intraocular lens size (difference from haptic to haptic) decreased significantly in eyes with only an IOL compared with normal controls or eyes with both an IOL and CTR. CONCLUSIONS: The CTR preserved the integrity of the capsular bag diameter, capsular opening, and IOL shape. It is likely that CTR implantation can avert contracture of the capsular bag and capsular opening, preventing IOL decentration.

Inhibitory effect of 2'-O-benzoylcinnamaldehyde on vascular endothelial cell proliferation and migration.

PURPOSE: To evaluate the inhibitory effect of the farnesyl transferase inhibitor 2'-O-benzoylcinnamaldehyde (CB 2'-ph) on proliferation and migration of vascular endothelial cells. METHODS: Bovine lens epithelial cells, bovine corneal endothelial cells, bovine keratocytes, bovine aortic endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) were treated with CB 2'-ph to determine its cell type specificity and antiproliferative effect. For inhibition of vascular endothelial cell growth factor (VEGF)- or basic fibroblast growth factor (bFGF)-induced proliferation of HUVECs, these cells were treated with various concentrations of CB 2'-ph. To assess the proliferation, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used. The migration assay was also performed to determine the effect of CB 2'-ph on HUVECs. The distance of HUVEC outgrowth was measured from the scraped edge of a monolayer after treatment with CB 2'-ph concentrations of 0, 1.5 and 2.5 microg/ml for 24, 48 and 72 h. RESULTS: The CB 2'-ph had an inhibitory effect on all tested types of cell proliferation but only HUVEC and BAEC proliferation was specifically inhibited in a dose-dependent manner. In addition, CB 2'-ph inhibited VEGF- or bFGF-induced proliferation and migration of HUVECs in a dose-dependent manner. CONCLUSIONS: These results indicate that CB 2'-ph, a farnesyl transferase inhibitor is thought to be an effective inhibitor of vascular endothelial cell proliferation and migration.