Design of Cathode Coating Using Niobate and Phosphate Hybrid Material for Sulfide-Based Solid-State Battery.

Coating the surface of the cathode active material of all-solid-state batteries with sulfide-based solid electrolytes is key for improving and enhancing the battery performance. Although lithium niobate (LiNbO3) is one of the most representative coating materials, its low durability at a highly charged potential and high temperature is an impediment to the realization of high-performance all-solid-state batteries. In this study, we developed new hybrid coating materials consisting of lithium niobate (Li-Nb-O) and lithium phosphate (Li-P-O) and investigated the influence of the ratio of P/(Nb + P) on the durability performance. The cathode half-cells, using a sulfide-based solid electrolyte Li6PS5Cl/cathode active material, LiNi0.5Co0.2Mn0.3O2, coated with the new hybrid coating materials of LiPxNb1-xO3 (x = 0-1), were exposed to harsh conditions (60 °C and 4.55 V vs Li/Li+) for 120 h as a degradation test. P substitution resulted in higher durability and lower interfacial resistance. In particular, the hybrid coating with x = 0.5 performed better, in terms of capacity retention and interfacial resistance, than those with other compositions of niobate and phosphate. The coated cathode active materials were analyzed using various analytical techniques such as scanning electron microscopy/energy-dispersive X-ray spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy (XAS) to elucidate the improvement mechanism. Moreover, the degraded cathodes were observed using time-of-flight secondary-ion mass spectrometry, TEM/electron diffraction, and XAS. These analyses revealed that the Nb-O-P coordination in the hybrid coating material captured O by P. The coordination suppressed the release of O from the coating layer as a decomposition side reaction to realize a higher durability than that of LiNbO3.

Rare Median Cleft-Lip Repair With Novel Surgical Procedures Using Bilateral Cleft Margin Flaps.

Reports of median cleft lip with nasal anomalies are few, and descriptions of concomitant surgical repair of a median cleft lip and bifid nose deformity are similarly rare. These surgical repair techniques mainly involve the use of normal neighboring structures. Reconstruction of the columella and nasal base is especially important. A new surgical procedure was examined using bilateral cleft margin flaps for patients with a rare median cleft lip. Two patients with a rare median cleft lip were indicated for the procedure. One patient was 3 months old at surgery, and the other patient was 6 months old. These patients underwent single-stage reconstruction of the lip and nose. The new surgical procedure is characterized by the reconstruction of the columella, which involves creating a supportive structure using a cleft margin flap; subsequently, an anterior covering is created using a hinge flap from the nasal tip. Upper lip formation is performed by repair of the orbicularis oris muscle and rotation advancement of a cutaneous and mucosal flap from the lateral segments. The postoperative follow-up period was 4 to 5 years. The postoperative appearance was satisfactory in both patients. Furthermore, no significant complications were observed postoperatively. In conclusion, the surgical procedure with bilateral cleft margin flaps described in this report allows for successful reconstruction of a median cleft lip. This procedure is effectively tissue saving and results in satisfactory outcomes, which are maintained over a long term.

Long-term functional and aesthetic evaluation of using a single rhomboid-shaped fascial strip for severe congenital unilateral blepharoptosis.

PURPOSE: Surgery for congenital blepharoptosis is often performed at approximately 4-5 years of age. A long-term follow-up is important during facial growth. We performed frontal suspension by using a single rhomboid-shaped autogenous fascial strip. We conducted a long-term evaluation of patients with severe congenital unilateral blepharoptosis. PATIENTS AND METHODS: A total of 334 patients with congenital blepharoptosis underwent surgery between 1994 and 2006. Of these, 192 patients had unilateral blepharoptosis with levator function less than 3 mm. A retrospective analysis was conducted on those patients who could be followed up postoperatively for at least 10 years and had accurate clinical photographs available. Visual acuity, palpebral fissure height (PFH), and marginal reflex distance (MRD) were evaluated from the photographs to compare both eyes. PFH and MRD were assessed as ratio. Morphological evaluation was based on patient and family comments. Statistical analysis included the t-test. RESULTS: Participants comprised 95 patients (63 male and 32 female; 43 left and 52 right). Visual acuity showed improvements. Although the postoperative MRD ratio of the affected eye was significantly improved, no clinically significant bilateral difference was seen in postoperative PFH, compared with those in the unaffected side. The surgical results were as follows: 62 excellent, 14 good, 12 fair, 3 poor, and 4 other cases in our criteria. No major complications occurred. Satisfactory result could be seen in 76 of the 95 cases. CONCLUSION: The evaluation results show that our surgical procedure appears useful for patients with unilateral congenital ptosis. Moreover, blepharoptosis surgery is useful for improving visual acuity. In this paper, we report this surgical procedure and discuss its long-term results.

Our Surgical Repair for Macrostomia with Two Novel Small Triangular Flaps: Long-Term Follow-Up and Results.

The surgical methods for repairing congenital macrostomia should be carefully selected from both functional and aesthetic points of view. The surgical correction of macrostomia results in normal orbicularis oris function and symmetry of the repaired lip. In this article, the authors report their novel technique and the results obtained, assessed retrospectively. Twelve primary cases of macrostomia underwent surgical repair between 1996 and 2013. The age at surgery ranged from 3 to 78 months. The authors' operative procedure uses two small triangular flaps with a superficial layer of orbicularis muscle to preserve the dynamic action of muscle fibers attached to the skin of the triangular flaps, with suturing across the orbicularis muscle bundles. The optimal length of a medial small triangular flap is 1.5 to 2.0 mm, and the length of a lateral flap is 5 to 8 mm. Evaluation was based on the degree of symmetry of the lips as a ratio of the affected side to the unaffected side, and the scar characteristics. The follow-up period in this retrospective study ranged from 3 to 21 years. The same method was applied to all 12 cases in the reconstruction of a natural appearance and dynamic function of the oral commissure, and the results over several years showed satisfactory outcomes. The authors' technique is very useful in the primary surgery for macrostomia, as the dynamic action of muscle fibers is preserved, if the muscle is not dissected from the skin in the cleft margin that includes the two medial small triangular flaps. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Frontal Hyperostosis in the Patients of Craniosynostosis After Cranial Distraction Osteogenesis.

BACKGROUND: Conventional fronto-orbital advancement and distraction osteogenesis (DOG) have been used to treat craniosynostosis, both of which are considered effective. During the authors' practice, a phenomenon of frontal hyperostosis has been observed in the patients of craniosynostosis after DOG, which has yet to be reported in the literature. The purpose of this study is trying to identify the factors related to the phenomenon. MATERIALS AND METHODS: From 1997 to 2010, all patients of craniosynostosis undergoing DOG were reviewed. The patient's age at operation, consolidation period, numbers of distractor, distance of distraction, and duration from removal of the distractors to identification of the phenomenon on computed tomography were recorded. The phenomenon was considered positive when the hyperostosis appeared on the frontal bone, where it was neither the osteotomy site nor the previous position of distractor. RESULTS: A total of 61 patients were included in this study, including 26 syndromic and 35 nonsyndromic patients. Two syndromic and 6 nonsyndromic patients had the phenomenon. There was no statistical difference between the patients with and without the phenomenon in comparison with the age, number of the distractor, consolidation period, and the distance of distraction. CONCLUSION: Frontal hyperostosis happened in some patients of craniosynostosis after DOG. Although no significant difference was demonstrated, the incidence of hyperostosis was higher in nonsyndromic patients and the patients of hyperostosis had shorter distance of distraction in both syndromic and nonsyndromic groups. Although the definite cause was unknown, we should pay attention to the phenomenon after distraction.

Importance of evaluating for cow's milk allergy in pediatric surgical patients with functional bowel symptoms.

BACKGROUND: Cow's milk allergy (CMA) can cause functional bowel symptoms. This can lead to confusion and difficulty in managing pediatric surgical patients who also have CMA. We examined CMA's effect on the management of pediatric surgical patients in our institute. METHODS: With institutional review board approval, 14 pediatric surgical patients with CMA were reviewed. Cow's milk allergy was diagnosed according to clinical findings and stimulation index (normal range <300%) of the lymphocyte stimulation test. RESULTS: The main symptoms were abdominal distension (n = 10), vomiting (n = 6), constipation (n = 2), and apnea (n = 1). Stimulation index median value was 731% (range, 341%-2132%). Patients were divided into 3 groups. In group 1 (n = 8), persistent postoperative bowel symptoms were initially considered related to surgical diseases. Following CMA diagnosis, CM elimination therapy improved symptoms. In group 2 (n = 4), CMA was diagnosed concurrently with surgical disease, and elimination therapy was continued postoperatively. In group 3 (n = 2), the pathogenesis of bowel symptoms was initially attributed to CMA and later diagnosed as Hirschsprung's disease. CONCLUSIONS: A high index of suspicion regarding the possibility of concurrent CMA may be necessary to manage bowel symptoms in pediatric surgical patients.

A lithium superionic conductor.

Batteries are a key technology in modern society. They are used to power electric and hybrid electric vehicles and to store wind and solar energy in smart grids. Electrochemical devices with high energy and power densities can currently be powered only by batteries with organic liquid electrolytes. However, such batteries require relatively stringent safety precautions, making large-scale systems very complicated and expensive. The application of solid electrolytes is currently limited because they attain practically useful conductivities (10(-2) S cm(-1)) only at 50-80 °C, which is one order of magnitude lower than those of organic liquid electrolytes. Here, we report a lithium superionic conductor, Li(10)GeP(2)S(12) that has a new three-dimensional framework structure. It exhibits an extremely high lithium ionic conductivity of 12 mS cm(-1) at room temperature. This represents the highest conductivity achieved in a solid electrolyte, exceeding even those of liquid organic electrolytes. This new solid-state battery electrolyte has many advantages in terms of device fabrication (facile shaping, patterning and integration), stability (non-volatile), safety (non-explosive) and excellent electrochemical properties (high conductivity and wide potential window).

[Outcome of conjunctival autograft with amniotic membrane transplantation for recurrent pterygium].

PURPOSE: To investigate the outcome of conjunctival autograft with amniotic membrane transplantation without the use of mitomycin C for cases of recurrent pterygium. CASES AND METHODS: Thirty-nine eyes of 35 patients (aged 27 to 76 years) who underwent the surgical procedure for recurrent pterygium at Yamaguchi University Hospital from November 1998 to July 2007 were evaluated retrospectively from their medical records. Patients who did not undergo postoperative follow-up examination for at least 6 months were excluded. The mean number of prior surgeries was 2.9 (range, 2 to 10), and the mean +/- SD follow-up time was 42.0 +/- 29.6 months. RESULTS: Twenty seven of 29 eyes (93.1%) with recurrent grade 3 pterygium showed a reduction in the size of the new growth after surgery. The symblepharon improved postoperatively in 5 of 15 eyes (33.3%) and restriction of ocular movement improved in 11 of 24 eyes (45.8%). Most recurrences occurred within 6 months after surgery, although one case did not show a recurrence until 2 years postsurgery. CONCLUSION: Conjunctival autograft with amniotic membrane transplantation without the use of mitomycin C reduced the size of the recurrent pterygium. However, 6 of the 16 eyes (37.5%) required subsequent surgery, suggesting that the procedure has limitations. Mitomycin C should therefore possibly be considered for cases with severe symblepharon or restriction of ocular movement. In choosing the surgical procedure for recurrent pterygium, diplopia can be an important indicator of the severity of a symblepharon or restriction of ocular movement.

Protective effect of dexamethasone against hypoxia-induced disruption of barrier function in human corneal epithelial cells.

The corneal epithelium functions as a barrier to protect the cornea from external agents such as infectious organisms and toxins and thereby contributes to corneal homeostasis. The barrier function of epithelia is dependent on the formation of tight and adherens junctions between adjacent epithelial cells. We have previously shown that hypoxia disrupts the barrier function of cultured human corneal epithelial (HCE) cells by affecting tight junctions. We have now examined the effect of dexamethasone on this barrier disruption induced by hypoxia in HCE cells. Measurement of transepithelial electrical resistance revealed that the hypoxia-induced decrease in the barrier function of HCE cells was inhibited by dexamethasone in a concentration-dependent manner. The hypoxia-induced loss of the tight junction protein ZO-1 from the borders of adjacent HCE cells (as revealed by immunofluorescence analysis) as well as the hypoxia-induced down-regulation of ZO-1 expression (as revealed by immunoblot analysis) were also inhibited by dexamethasone, whereas this drug had no effect on the expression or distribution of the tight junction protein occludin or of the adherens junction proteins E-cadherin and ß-catenin. Moreover, dexamethasone attenuated the reorganization of the actin cytoskeleton, the formation of focal adhesions, and the up-regulation of myosin light chain kinase expression induced by hypoxia in HCE cells. Our results thus suggest that dexamethasone protects corneal epithelial cells from the hypoxia-induced disruption of barrier function by maintaining the distribution and expression of ZO-1 as well as the organization of the actin cytoskeleton.

Protection of human corneal epithelial cells from hypoxia-induced disruption of barrier function by hepatocyte growth factor.

The barrier function of the corneal epithelium maintains corneal homeostasis and is mediated by tight junctions (TJs) and adherens junctions (AJs). It is also susceptible to disruption by hypoxia. We have now examined the effects of hypoxia on TJs and AJs as well as on barrier function in human corneal epithelial (HCE) cells. Moreover, we investigated whether such effects of hypoxia might be modulated by hepatocyte growth factor (HGF). The subcellular distribution of the TJ proteins ZO-1 and occludin, the AJ proteins E-cadherin and beta-catenin, and actin filaments was examined by fluorescence microscopy. The abundance of junctional proteins as well as of myosin light chain kinase (MLCK) was determined by immunoblot analysis. Barrier function was evaluated by measurement of transepithelial electrical resistance (TER). Hypoxia-induced both the disappearance of ZO-1 from the borders of neighboring HCE cells as well as the down-regulation of ZO-1 expression without affecting the distribution or abundance of occludin, E-cadherin, or beta-catenin. It also induced the formation of actin stress fibers, the up-regulation of MLCK expression, and a reduction in the TER of HCE cells. All these effects of hypoxia were inhibited by HGF. Neither hypoxia nor HGF exhibited a mitogenic or cytotoxic effect on HCE cells. HGF thus protects HCE cells from hypoxia-induced disruption of barrier function by maintaining the expression and distribution of ZO-1. Inhibition of the effects of hypoxia on the organization of the actin cytoskeleton might also contribute to this protective action of HGF.

In vivo observation of Langerhans cells by laser confocal microscopy in Thygeson's superficial punctate keratitis.

PURPOSE: To characterize the cornea of individuals with Thygeson's superficial punctate keratitis (TSPK) at the cellular level by laser confocal biomicroscopy. METHODS: Both corneas of three patients with TSPK referred to Yamaguchi University Hospital were imaged with a laser confocal biomicroscope. Morphological changes were evaluated for each layer of the cornea. RESULTS: The number of Langerhans cells was greatly increased in the basal cell layer of the focal corneal epithelium and in Bowman's layer in the four eyes affected by TSPK. Aggregates of these cells were associated with the subepithelial nerve plexus. Langerhans cells were also evident in the unaffected eyes of the two patients with unilateral TSPK, although their numbers were much smaller than those in the affected eyes. Topical treatment with betamethasone phosphate resulted in the virtual disappearance of Langerhans cells from the affected eyes. CONCLUSION: The prominent association of Langerhans cells with TSPK suggests that the activation of these cells by inflammatory conditions might contribute to the pathogenesis of this disorder.

Double mutation (R124H, N544S) of TGFBI in two sisters with combined expression of Avellino and lattice corneal dystrophies.

PURPOSE: The R124H mutation of the keratoepithelin gene (TGFBI) causes Avellino corneal dystrophy whereas the N544S mutation of this same gene gives rise to lattice corneal dystrophy. We now report two cases with both R124H and N544S mutations of TGFBI. METHODS: Genomic DNA and cDNA were isolated from the proband and family members and were subjected to polymerase chain reaction-mediated amplification of exons 1-17 of TGFBI. The amplification products were directly sequenced. Allele-specific cloning and sequencing were applied to evaluate the compound heterozygous mutation. RESULTS: Molecular genetic analysis revealed that the proband and one sister harbored both a heterozygous CGC-->CAC (Arg-->His) mutation at codon 124 and a heterozygous AAT-->AGT (Asn-->Ser) mutation at codon 544 of TGFBI. Slit-lamp examination revealed multiple granular regions of opacity and lattice lines in the corneal stroma of the proband and her sister with the double mutation. Allele-specific cloning and sequencing revealed that the R124H and N544S mutations are on different chromosomes. CONCLUSIONS: As far as we are aware, this is the first report of a patient with a double mutation (R124H, N544S) of TGFBI causing an autosomal dominant form of corneal dystrophy. The clinical manifestations of the two cases with both R124H and N544S mutations appeared to be a summation of Avellino and lattice corneal dystrophies.

Protection of human corneal epithelial cells from hypoxia-induced disruption of barrier function by keratinocyte growth factor.

PURPOSE: The possible detrimental effect of hypoxia on the barrier function of corneal epithelial cells and whether keratinocyte growth factor (KGF) might protect against such an effect were investigated. METHODS: Simian virus 40-transformed human corneal epithelial (HCE) cells were cultured for 4 days to allow the establishment of barrier function. They were then deprived of serum for 24 hours before exposure to 1% (hypoxia) or 21% (normoxia) oxygen for 24 hours. Barrier function was evaluated by measurement of transepithelial electrical resistance (TER). The localization of ZO-1 and occludin was determined by immunofluorescence microscopy, and the expression of these tight junctional proteins as well as the phosphorylation of the mitogen-activated protein kinases ERK, p38, and JNK were examined by immunoblot analysis. RESULTS: Hypoxia induced a decrease in the TER of HCE cells compared with that of cells maintained under normoxia. The localization of ZO-1 at cell-cell borders was disrupted by hypoxia, whereas the distribution of occludin was not affected. Hypoxia also induced the downregulation of ZO-1 and a decrease in the phosphorylation of ERK without affecting the phosphorylation of p38 or JNK. All these effects of hypoxia were inhibited by KGF. The effects of KGF on TER and ZO-1 localization in cells exposed to hypoxia were inhibited by PD98059, an inhibitor of ERK signaling. Neither hypoxia nor KGF exhibited mitogenic or cytotoxic effects in HCE cells. CONCLUSIONS: Hypoxia induces disruption of the barrier function of HCE cells by eliciting the redistribution and degradation of ZO-1, and this effect is inhibited by KGF in a manner dependent on ERK activation.

Delayed disruption of barrier function in cultured human corneal epithelial cells induced by tumor necrosis factor-alpha in a manner dependent on NF-kappaB.

PURPOSE: The corneal epithelium provides a barrier that is both important for corneal homeostasis and dependent on tight junctions (TJs) between adjacent epithelial cells. The authors examined the effects of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, on barrier function and the expression of TJ proteins in simian virus 40-transformed human corneal epithelial (HCE) cells. METHODS: The barrier function of cultured HCE cells was evaluated by measurement of transepithelial electrical resistance (TER). The subcellular distribution of the TJ proteins zonula occludens-1 (ZO-1) and occludin and that of the p65 subunit of nuclear factor-kappaB (NF-kappaB) were determined by immunofluorescence staining. The expression of ZO-1 and occludin and the phosphorylation and degradation of the NF-kappaB inhibitory protein IkappaB-alpha were examined by immunoblot analysis. RESULTS: TNF-alpha induced a decrease in the TER of HCE cells in a concentration- and time-dependent manner. It also induced the disappearance of ZO-1 from the interfaces of neighboring HCE cells without affecting the localization of occludin. The abundance of neither ZO-1 nor occludin was affected by TNF-alpha. TNF-alpha induced the phosphorylation and downregulation of IkappaB-alpha and the translocation of the p65 subunit of NF-kappaB to the nucleus. The NF-kappaB inhibitor curcumin blocked the effects of TNF-alpha on TER and the subcellular localization of ZO-1 at late phase. CONCLUSIONS: TNF-alpha disrupted the barrier function of HCE cells, apparently by affecting the localization of ZO-1 at TJs in a manner dependent on NF-kappaB at late phase. This action of TNF-alpha may contribute to the loss of corneal epithelial barrier function associated with ocular inflammation.

Second-harmonic imaging microscopy of normal human and keratoconus cornea.

PURPOSE: The purpose of this study was to evaluate the ability of second-harmonic imaging to identify differences in corneal stromal collagen organization between normal human and keratoconus corneas. METHODS: Six normal corneas from eye bank donors and 13 corneas of patients with keratoconus, obtained after penetrating keratoplasty were examined. A femtosecond titanium-sapphire laser with 800-nm output was used to generate second-harmonic signals collected at 400 nm from central and paracentral corneal tissue blocks. Three-dimensional (3-D) data sets were collected and reconstructed to evaluate the location and orientation of stromal collagen lamellae. RESULTS: Imaging of second-harmonic signals combined with 3-D reconstruction of the normal cornea identified a high degree of lamellar interweaving, particularly in the anterior cornea. Of note was the detection of lamellae that inserted into Bowman's layer and were oriented transverse to the corneal surface, penetrating posteriorly approximately 120 mum. In keratoconus corneas, imaging second-harmonic signals identified less lamellar interweaving and a marked reduction or loss of lamellae inserting into Bowman's layer in 12 of 13 cases, particularly in regions associated with cone development without breaks in Bowman's layer or scarring. CONCLUSIONS: Compared with normal adult corneas, marked abnormalities were detected in the organization of the anterior corneal collagen lamellae of keratoconus corneas by second harmonic imaging. These structural abnormalities are consistent with the known changes in collagen organization and biomechanical strength of keratoconus.

Stimulation of corneal epithelial migration by a synthetic peptide (PHSRN) corresponding to the second cell-binding site of fibronectin.

PURPOSE: Fibronectin plays an important role in the migration of corneal epithelial cells in vivo. The Arg-Gly-Asp (RGD) sequence in the principal cell binding domain of fibronectin mediates the interaction of fibronectin with integrins, whereas the Pro-His-Ser-Arg-Asn (PHSRN) sequence of fibronectin is thought to modulate this interaction. The authors examined the effects of a PHSRN peptide on corneal epithelial migration in vitro and in vivo. METHODS: Epithelial migration in vitro was examined with the rabbit cornea in organ culture. The motility and phenotype of simian virus 40-transformed human corneal epithelial (HCE) cells were evaluated by time-lapse and immunofluorescence microscopy, respectively. Tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin was examined by immunoprecipitation and immunoblot analysis. The healing of rabbit corneal epithelial wounds induced by 1-heptanol was evaluated by fluorescein staining. RESULTS: The PHSRN peptide stimulated corneal epithelial migration in organ culture in a concentration-dependent manner, and it increased HCE cell motility in vitro. The peptide induced the accumulation of F-actin and the formation of focal adhesions at the leading edge of HCE cells. It also upregulated the tyrosine phosphorylation of FAK and paxillin in HCE cells, but it did not affect HCE cell proliferation or attachment to a fibronectin matrix. Administration of the PHSRN peptide in eye drops promoted corneal epithelial wound closure in vivo in a dose-dependent manner. None of these effects of the PHSRN peptide were induced by a control NRSHP peptide. CONCLUSIONS: The PHSRN peptide mimics many of the effects of fibronectin on corneal epithelial cells and may prove suitable as a substitute for fibronectin in the treatment of persistent corneal epithelial defects.

Role of Rac1 in fibronectin-induced adhesion and motility of human corneal epithelial cells.

PURPOSE: The fibronectin-integrin system plays an important role in adhesion and migration of corneal epithelial cells and thereby contributes to epithelial wound healing. The role of Rac1, a member of the Rho family of GTPases, in the intracellular signaling responsible for regulation of the adhesion and motility of corneal epithelial cells by fibronectin was examined. METHODS: Simian virus 40-transformed human corneal epithelial (HCE) cells were plated on fibronectin or on bovine serum albumin as a control. Cell motility was monitored by time-lapse video microscopy. The actin cytoskeleton and focal adhesions were detected by staining of cells with rhodamine-phalloidin and antibodies to phosphotyrosine, respectively. The activation of Rac1 and phosphorylation of its effector PAK were evaluated with a pull-down assay and immunoblot analysis, respectively. The effects of mutant forms of Rac1 were determined by cell transfection. RESULTS: HCE cells plated on fibronectin manifested greater levels of cell adhesion and motility than did those plated on bovine serum albumin. Fibronectin also induced the accumulation of F-actin and the formation of focal adhesions at the cell periphery as well as the activation of Rac1 and the phosphorylation of PAK. Expression of the dominant negative mutant Asn17Rac1 inhibited the effects of fibronectin on cell adhesion and motility, the actin cytoskeleton, and focal adhesions. Expression of the constitutive active mutant Val12Rac1 mimicked the effects of fibronectin on F-actin and focal adhesions. CONCLUSIONS: Rac1 is necessary for the promotion of HCE cell adhesion and motility by fibronectin. It therefore probably plays an important role in corneal wound healing.

Promotion of corneal epithelial wound healing by a tetrapeptide (SSSR) derived from IGF-1.

PURPOSE: A prior study showed that a tetrapeptide (FGLM-amide) derived from the carboxyl terminus of substance P (SP) and a 12-residue peptide corresponding to the C domain of insulin-like growth factor (IGF)-1 mimic the synergistic effect of the full-length molecules on corneal epithelial wound healing. To develop an effective treatment for persistent corneal epithelial defects, the current study was conducted to investigate the minimal sequence within the C domain of IGF-1 that is required for such synergism with SP or FGLM-amide. METHODS: The effects of IGF-1-derived peptides on corneal epithelial migration were evaluated with a rabbit corneal organ-culture system. RESULTS: A tetrapeptide (SSSR; Ser(33)-Ser-Ser-Arg) derived from the C domain of IGF-1 was sufficient for the synergistic promotion with FGLM-amide both of corneal epithelial migration in vitro and of wound closure in vivo. The activity of the SSSR peptide was sequence specific and its potency was similar to that of IGF-1. The SSSR peptide by itself also promoted corneal epithelial migration in vitro at higher concentrations. It was devoid, however, of both the mitogenic action of IGF-1 and the ability of the full-length molecule to induce neovascularization. CONCLUSIONS: The SSSR sequence mediates the synergistic effect of IGF-1 with SP on corneal epithelial wound healing. Clinical application of the SSSR peptide would be expected to be free of potentially deleterious side effects associated with treatment with full-length IGF-1. Local administration of the SSSR tetrapeptide, alone or in combination with FGLM-amide, is thus a potential new strategy for the treatment of nonhealing epithelial wounds.

Delayed corneal epithelial wound healing after penetrating keratoplasty in individuals with lattice corneal dystrophy.

PURPOSE: To investigate whether corneal epithelial cells of individuals with lattice corneal dystrophy (LCD) possess an intrinsic defect. DESIGN: Retrospective case-control study. METHODS: The medical charts of nine individuals with LCD and those of 14 patients with keratoconus and 11 patients with corneal leukoma (controls), all of whom underwent penetrating keratoplasty (PKP) in one eye at Yamaguchi University Hospital between February 1998 and November 2001, were examined for the time for epithelial resurfacing after surgery. RESULTS: The time required for resurfacing of the corneal epithelium after PKP was significantly greater in LCD patients (8.56 +/- 4.95 days, mean +/- SD) than in patients with either keratoconus (1.71 +/- 0.91 days, P = .006) or corneal leukoma (3.00 +/- 1.95 days, P = .03). CONCLUSIONS: Corneal epithelial wound healing was delayed in LCD patients after PKP, suggesting that the keratoepithelin gene mutations responsible for this condition affect corneal epithelial cells.

Modification of a soft contact lens for use during irrigation and aspiration in the penetrating keratoplasty triple procedure.

The purpose of the present study was to design and test a new soft contact lens with 2 holes for improvement of both visibility and the rate of lens cortex aspiration during cataract surgery using the penetrating keratoplasty triple procedure. Two groups of 9 age-matched patients underwent the penetrating keratoplasty triple procedure with or without the newly designed contact lens. The use of the new soft contact lens reduced the time required for irrigation and aspiration of the lens cortex from 183.8 +/- 92.2 to 121.2 +/- 27.9 seconds (P<.05); the total operative and open-sky times also significantly decreased. In addition, use of the lens greatly improved visibility of the surgical field during cataract extraction. The newly designed soft contact lens thus improves management of the lens cortex during the penetrating keratoplasty triple procedure.