Membrane Contraction Research Articles

Adjunctive effect of intravitreal bevacizumab prior to lens-sparing vitrectomy in aggressive posterior retinopathy of prematurity: a case report

Intravitreal injection of bevacizumab in retinopathy of prematurity has shown satisfactory results without any systemic complications. However, increased fibrosis and tissue contraction are reported as adverse effects in some cases. A premature girl, born at 29 weeks + 4 days of gestation, had bilateral aggressive posterior retinopathy of prematurity (APROP) on her first screening at 3 weeks of age. She received extensive, near confluent, laser ablation of the avascular retina and off-label intravitreal bevacizumab (0.75 mg) injection OU. The right eye showed a slight regression, but a localized tractional membrane was noted OS. After another intravitreal bevacizumab injection in each eye, the left eye underwent lens-sparing vitrectomy (LSV) because of contraction of the proliferative membrane leading to a dome-shaped tractional retinal detachment (TRD). At 6-week follow-up, the left eye showed complete retinal reattachment. Both eyes showed prompt resolution of vascular engorgement with anterior progression of the peripheral retinal vasculature. Intravitreal bevacizumab is safe and effective as a treatment of APROP. In some cases tissue contraction may occur, but because TRD is localized to the posterior pole, effective LSV can be performed.

온도 변화 방법을 이용한 조미계란의 신속 가염 방법

Abstract This study developed a rapid egg-salting method using a temperature change in NaCl solution under pressure. The permeation effects(PEs) of NaCl into eggs at ambient pressure were analyzed 1) after soaking them in 20, 30, or 40%(w/v) NaCl solution at 50℃ and 2) after soaking in 20 ～ 40% concentrations(w/v) of NaCl solution at 4℃ immediately after soaking at 50°C for 1 hr(temperature change method; TCM). Under permeation conditions(40% NaCl solution with TCM), the PE of NaCl into eggs at various pressures(4.0 ～ 7.0 MPa) was determined. The PE improved with increasing NaCl concentration and pressure. In 40%(w/v) NaCl solution, the PE was more rapid with TCM(0.70% for 2 hr) than without TCM(0.60% for 2 hr). At 7.0 MPa pressure, the PE was more rapid with TCM(1.66% for 15 min) than without TCM(1.40% for 15 min). These results suggest that the TCM-induced contraction of the egg membrane improved the PE. Therefore, we believe that the development of a rapid salting method for seasoning eggs is possible with the TCM.Key words: egg, rapid salting, temperature change, seasoning, soaking

Spontaneous closure of stage IV idiopathic full-thickness macular hole and late reopening as a lamellar macular hole: a case report

IntroductionSpontaneous closure of traumatic macular holes is described as a common event in the peer-reviewed literature. However, the spontaneous closure of stage III and IV full-thickness idiopathic macular holes has been reported in less than 15 cases in the literature, this being an extremely rare event, with their reopening being even more infrequent. We report a case of a spontaneous closure of stage IV idiopathic full-thickness macular hole and late reopening as a lamellar macular hole.Case presentationA 67-year-old Spanish man was referred to our hospital with a complaint of decreased vision in his right eye and metamorphopsia for approximately 11 months. He did not report any trauma. Diagnosis was based on fundoscopic and optical coherence tomography. They revealed a stage IV full-thickness idiopathic macular hole and a small epiretinal membrane. Three months later the hole spontaneously closed, and two years later we appreciated its reopening as a lamellar macular hole.ConclusionsThe contraction of the epiretinal membrane could have contributed to cystic spaces and their fusion, subsequently, to the formation of a lamellar macular hole. To the best of our knowledge this is the first report in the literature of a spontaneously closed full-thickness idiopathic macular hole with reopening as a partial thickness macular defect.

SD-OCT Imaging of Idiopathic Macular Holes With Spontaneous Closure

Spectral-domain optical coherence tomography serial changes in three cases of spontaneous closure of idiopathic macular hole at stages II, III, and IV are described. Initial and serial spectral-domain optical coherence tomography images document the progressive closure. Macular holes apparently resolved spontaneously through two different mechanisms: posterior hyaloid detachment in case 1 and a contraction of epiretinal macular membrane in cases 2 and 3. The spontaneous closure of idiopathic full-thickness macular holes may occur in any stage of idiopathic macular hole; the small size of the hole is a common feature in all cases of spontaneous closure reported.

Active reinforcement of externally imposed folding in amphibians embryonic tissues

Although the folding of epithelial layers is one of the most common morphogenetic events, the underlying mechanisms of this process are still poorly understood. We aimed to determine whether an artificial bending of an embryonic cell sheet, which normally remains flat, is reinforced and stabilized by intrinsic cell transformations. We observed both reinforcement and stabilization in double explants of blastocoel roof tissue from Xenopus early gastrula embryos. The reinforcement of artificial bending occurred over the course of a few hours and was driven by the gradual apical constriction and radial elongation of previously compressed cells situated at the bending arch of the concave layer of explant. Apical constriction was associated with actomyosin contraction and endocytosis-mediated engulfing of the apical cell membranes. Cooperative apical constrictions of the concave layer of cells produced a tensile force that extended over the entire surface of the explant and correlated with apical contraction of the concave side cells. In the explants taken from the anterior regions of the embryo, this reinforcement was more stable and the bending better expressed than in those taken from suprablastoporal areas. The morphogenetic role of cell responses to the bending force is discussed.

Preparation and characterization of electrospun poly (lactide-co-glycolide) membrane with different L-lactide and D-lactide ratios

Poly (lactide-co-glycolide) (PLGA, LA/GA = 80/20) with different L-lactide and D-lactide molar ratio (L-LA/D-LA = 1.0∼0.5) has been synthesized, and electrospun into nanofibrous membranes. The obtained copolymers were characterized by 1HNMR, Polarimeter, GPC and DSC. The relationship between the contraction of the membranes and the L-LA/D-LA ratio of copolymers has been investigated through DSC, SEM and XRD. The results indicated that with the L-LA/D-LA ratio decreasing, the crystal fragments in copolymer decreased significantly even disappeared; meanwhile, the contraction of the membranes in PBS at 37 °C increased. The mechanism of the contraction of electrospun PLGA membrane during incubated is proposed based on the present results.

Retinal Pigment Epithelium and Müller Progenitor Cell Interaction Increase Müller Progenitor Cell Expression of PDGFR and Ability to Induce Proliferative Vitreoretinopathy in a Rabbit Model

Purpose. Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment characterized by redetachment of the retina as a result of membrane formation and contraction. A variety of retinal cells, including retinal pigment epithelial (RPE) and Müller glia, and growth factors may be responsible. Platelet-derived growth factor receptor alpha (PDGFRα) is found in large quantities in PVR membranes, and is intrinsic to the development of PVR in rabbit models. This study explores the expression of PDGFR in cocultures of RPE and Müller cells over time to examine how these two cell types may collaborate in the development of PVR. We also examine how changes in PDGFRα expression alter Müller cell pathogenicity. Methods. Human MIO-M1 Müller progenitor (MPC) and ARPE19 cells were studied in a transmembrane coculture system. Immunocytochemistry and Western blot were used to look at PDGFRα, PDGFRβ, and GFAP expression. A transfected MPC line cell line expressing the PDGFRα (MIO-M1α) was generated, and tested in a rabbit model for its ability to induce PVR. Results. The expression of PDGFRα and PDGFRβ was upregulated in MIO-M1 MPCs cocultured with ARPE19 cells; GFAP was slightly decreased. Increased expression of PDGFRα in the MIO-M1 cell line resulted in increased pathogenicity and enhanced ability to induce PVR in a rabbit model. Conclusions. Müller and RPE cell interaction can lead to upregulation of PDGFRα and increased Müller cell pathogenicity. Müller cells may play a more active role than previously thought in the development of PVR membranes, particularly when stimulated by an RPE-cell-rich environment. Additional studies of human samples and in animal models are warranted.

Cofilin-Mediated F-Actin Severing Is Regulated by the Rap GTPase and Controls the Cytoskeletal Dynamics That Drive Lymphocyte Spreading and BCR Microcluster Formation

When lymphocytes encounter APCs bearing cognate Ag, they spread across the surface of the APC to scan for additional Ags. This is followed by membrane contraction and the formation of Ag receptor microclusters that initiate the signaling reactions that lead to lymphocyte activation. Breakdown of the submembrane cytoskeleton is likely to be required for the cytoskeleton reorganization that drives cell spreading and for removing physical barriers that limit Ag receptor mobility. In this report, we show that Ag receptor signaling via the Rap GTPases promotes the dephosphorylation and activation of the actin-severing protein cofilin and that this results in increased severing of cellular actin filaments. Moreover, we show that this cofilin-mediated actin severing is critical for the changes in actin dynamics that drive B and T cell spreading, for the formation of BCR microclusters, and for the increased mobility of BCR microclusters within the plasma membrane after BCR engagement. Finally, using a model APC, we show that activation of this Rap-cofilin signaling module controls the amount of Ag that is gathered into BCR microclusters and that this is directly related to the magnitude of the resulting BCR signaling that is initiated during B cell-APC interactions. Thus, Rap-dependent activation of cofilin is critical for the early cytoskeletal changes and BCR reorganization that are involved in APC-dependent lymphocyte activation.

This issue of Acta, printed and electronic

The cover illustration shows a painting of Allvar Gullstrand painted in 1915, 4 years after he received the Nobel Prize for medicine. This issue is dedicated to the centennial of Allvar Gullstrand’s Nobel Prize. He is the only ophthalmologist ever to receive this prestigious price. Stefan Seregard writes an editorial commemorating this event. This is followed by an historical article by Ehinger and Grzybowski on the life and times of Allvar Gullstrand. Yilmaz et al. in USA, Spain and Ireland review the use of intravitreal bevacizumab for diabetic macular oedema. This is an extensive review of the literature for this new and important treatment modality. Lundström et al. in Sweden and Australia found the Catquest questionnaire useful for measuring self-assessed visual function before and after cataract surgery. Mönestam and Behndig found that light scattering and glistening in intraocular lenses does not affect visual acuity. Gazieva et al. in Denmark performed LASIK with two types of laser systems, both which effectively reduce high degrees of myopia with reasonable but slightly different predictability. Rijneveld et al. in the Netherlands found that emergency corneal grafts fail mostly due to host factors, not the quality of the donor tissue. Reinshagen et al. in Switzerland and Germany used mesenchymal stem cell in rabbits to treat total limbal stem cell deficiency. Heijl et al. in Sweden and USA report that intraocular pressure reduction with drug treatment depends on the baseline IOP level and suggest that the baseline IOP level should be documented when reporting treatment effect on intraocular pressure. Larsson et al. in Sweden used the Heidelberg retina tomography system to evaluate optic nerve heads in children. Lin et al. in Taiwan describe lacrimal canaliculitis in a series of patients. Mehlsen et al. in Denmark found that a calcium channel blocker and an angiotensin converting enzyme inhibitor did not influence retinal autoregulation in diabetic patients. Kook et al. in Germany found that intravitreal bevacizumab and/or triamcinolone do not provide long-term improvement for diabetic macular oedema. Kofoed et al. in Copenhagen found that hyperbaric oxygen exposure influenced electrophysiological components related to bipolar in Müller cells. It did not influence retinal thickness. Holton et al. in Denmark examined the influence of light source on contrast sensitivity in patients with AMD. They found that full spectral radiance incandescent light sources seem optimal. Available on http://www.actaophthalmologica.com Stalmans and a large international group review extensively the use of colour Doppler imaging in ocular blood flow research. Founti et al. in Greece and USA found good reproducibility between technicians in imaging retrobulbar blood flow in healthy volunteers. Frøen et al. in Norway and Hungary found that cells from the iris pigment epithelium have limited capabilities as retinal stem cells. Andjelić et al. in Slovenia found that lens capsule contraction with changing in calcium levels or mechanical stimulus. Sieving in USA explains Medline indexing and keywords. Bull in Bergen proposes that fireworks should be banned to reduce eye injuries. Basit et al. in Trondheim describe a case of Wernicke’s encephalopathy in a young boy. Russo et al. in Liverpool found scleral calcification in a case of recurrent melanoma after brachytherapy. Rama et al. in Italy report severe keratitis following corneal cross-linking for keratoconus. Jonas and Jonas in Germany compare peripapillary scleral thickness in glaucoma patients and normal subjects. Lim and An in Korea report good results after epiretinal membrane removal. Kernt et al. in Germany had good experiences with focal and panretinal photocoagulation with a navigated laser. Fielden et al. in Canada describe a cluster of cases with intraocular inflammation following bevacizumab injection. Bloch et al. in Denmark and Egypt describe neovascular membrane contraction and retinal pigment epithelial rupture following verteporfin and bevacizumab treatment. Caramoy et al. in Germany found recurrent choroidal neovascular membrane after autologous RPE transplantation. I wish all readers a Merry Christmas and a Happy New Year and hope that they enjoy reading ACTA during the holidays.

Presence of contracting cellular elements at the border of stage III and IV macular holes

AbstractPurpose Myofibroblasts play a major role in the production of retractile phenomena causing contraction or shrinkage of the epiretinal membranes (ERM) in proliferative vitreoretinopathy, diabetic retinopathy or idiopathic macular epiretinal membranes. The presence of a‐smooth muscle actin (a‐SMA)‐positive myofibroblasts and of ED‐A fibronectin (FN), one of the main inducers of myofibroblastic differentiation was studied in internal limiting membranes (ILM) removed during macular hole surgery.Methods Samples of ILMs following macular hole surgery in 9 eyes were collected. Double immunofluorescence staining with antibodies recognizing a‐SMA and ED‐A FN followed by confocal microscopy analysis as well as electronic microscopy were performed.Results a‐SMA and ED‐A FN were detected in ILM removed in stage III and IV macular holes. ED‐A FN was expressed in close relation with a‐SMA‐positive myofibroblasts predominately located close to the border of the macular hole area. Distally to the hole area the ILM specimens were a‐SMA and ED‐A FN negative. No a‐SMA staining was observed in ILM specimens of stage II macular hole specimens.Conclusion Scanning electron microscopy indicated that cellular migration was not apparent around the macular hole in the early stage of the development of this pathology.Cellular elements expressing contractile properties related to a‐SMA, typical of myofibroblasts differentiation, appear to be present at late stage macular holes.

Relationship between ATP-induced membrane potential and contraction in smooth muscle of chicken anterior mesenteric artery

Relationship between ATP-induced membrane potential and contraction in smooth muscle of chicken anterior mesenteric artery

An Eulerian/XFEM formulation for the large deformation of cortical cell membrane

Most animal cells are surrounded by a thin layer of actin meshwork below their membrane, commonly known as the actin cortex (or cortical membrane). An increasing number of studies have highlighted the role of this structure in many cell functions including contraction and locomotion, but modelling has been limited by the fact that the membrane thickness (about 1 μm) is usually much smaller than the typical size of a cell (10–100 μm). To overcome theoretical and numerical issues resulting from this observation, we introduce in this paper a continuum formulation, based on surface elasticity, that views the cortex as an infinitely thin membrane that can resists tangential deformation. To accurately model the large deformations of cells, we introduced equilibrium equations and constitutive relations within the Eulerian viewpoint such that all quantities (stress, rate of deformation) lie in the current configuration. A solution procedure is then introduced based on a coupled extended finite element approach that enables a continuum solution to the boundary value problem in which discontinuities in both strain and displacement (due to cortical elasticity) are easily handled. We validate the approach by studying the effect of cortical elasticity on the deformation of a cell adhering on a stiff substrate and undergoing internal contraction. Results show very good prediction of the proposed method when compared with experimental observations and analytical solutions for simple cases. In particular, the model can be used to study how cell properties such as stiffness and contraction of both cytoskeleton and cortical membrane lead to variations in cell's surface curvature. These numerical results show that the proposed method can be used to gain critical insights into how the cortical membrane affects cell deformation and how it may be used as a means to determine a cell's mechanical properties by measuring curvatures of its membrane.

Interleukin and Growth Factor Levels in Subretinal Fluid in Rhegmatogenous Retinal Detachment: A Case-Control Study

BackgroundRhegmatogenous retinal detachment (RRD) is a major cause of visual loss in developed countries. Proliferative vitreoretinopathy (PVR), an eye-sight threatening complication of RRD surgery, resembles a wound-healing process with inflammation, scar tissue formation, and membrane contraction. This study was performed to determine the possible involvement of a wide range of cytokines in the future development of PVR, and to identify predictors of PVR and visual outcome.MethodologyA multiplex immunoassay was used for the simultaneous detection of 29 different cytokines in subretinal fluid samples from patients with primary RRD. Of 306 samples that were collected and stored in our BioBank between 2001 and 2008, 21 samples from patients who developed postoperative PVR were compared with 54 age-, sex-, and storage-time–matched RRD control patients who had an uncomplicated postoperative course during the overall follow-up period.FindingsLevels of IL-1α, IL-2, IL-3, IL-6, VEGF, and ICAM-1 were significantly higher (P<0.05) in patients who developed postoperative PVR after reattachment surgery than in patients with an uncomplicated postoperative course, whereas levels of IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-11, IL-12p70, IL-13, IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-25, IL-33, TNF-α, IFN-γ, IGF-1, bFGF, HGF, and NGF were not (P>0.05). Multivariate logistic regression analysis revealed that IL-3 (P = 0.001), IL-6 (P = 0.047), ICAM-1 (P = 0.010), and preoperative visual acuity (P = 0.026) were independent predictors of postoperative PVR. Linear regression analysis showed that ICAM-1 (P = 0.005) and preoperative logMAR visual acuity (P = 0.001) were predictive of final visual outcome after primary RRD repair.Conclusions/SignificanceOur findings indicate that after RRD onset an exaggerated response of certain cytokines may predispose to PVR. Sampling at a time close to the onset of primary RRD may thus provide clues as to which biological events may initiate the development of PVR and, most importantly, may provide a means for therapeutic control.

Glucosamine inhibits epithelial-to-mesenchymal transition and migration of retinal pigment epithelium cells in culture and morphologic changes in a mouse model of proliferative vitreoretinopathy

To explore the effect of glucosamine (GlcN) on transforming growth factor (TGF)-β signalling and several processes involved in proliferative vitreoretinopathy (PVR). We evaluated the surface levels of TGF-β receptor and its binding of TGF-β in ARPE-19 cells. Release of cytokines and collagen, and expression of signalling intermediates were quantified. Migration was qualitatively and quantitatively examined. The morphology of cells undergoing PVR in vitro and in a mouse PVR model was observed. Glucosamine reduced the surface levels of TGF-β receptor and the ability of ARPE-19 cells to bind TGF-β. In ARPE-19 cells, TGF-β1 plus epidermal growth factor (EGF) or TGF-β2 increased the expression of alpha-smooth muscle actin (α-SMA) and decreased the expression of zona occludens protein (ZO-1). Transforming growth factor-(β2) also caused the release of platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF) and type 1 collagen and increased the phosphorylation of SMAD2 and SMAD3. Platelet-derived growth factor and CTGF stimulated cell migration, and TGF-β2 stimulated wound closure, contraction of collagen and changes in cell morphology. Treatment with GlcN counteracted all of these effects, and its administration in the mouse model reduced the morphologic appearance of PVR. Glucosamine could inhibit the TGF-β signalling pathway in retinal pigment epithelium cells and several of the downstream events associated with epithelial-mesenchymal transition and PVR.

Protein Kinase D Signaling: Multiple Biological Functions in Health and Disease

Protein kinase D (PKD) is an evolutionarily conserved protein kinase family with structural, enzymological, and regulatory properties different from the PKC family members. Signaling through PKD is induced by a remarkable number of stimuli, including G-protein-coupled receptor agonists and polypeptide growth factors. PKD1, the most studied member of the family, is increasingly implicated in the regulation of a complex array of fundamental biological processes, including signal transduction, cell proliferation and differentiation, membrane trafficking, secretion, immune regulation, cardiac hypertrophy and contraction, angiogenesis, and cancer. PKD mediates such a diverse array of normal and abnormal biological functions via dynamic changes in its spatial and temporal localization, combined with its distinct substrate specificity. Studies on PKD thus far indicate a striking diversity of both its signal generation and distribution and its potential for complex regulatory interactions with multiple downstream pathways, often regulating the subcellular localization of its targets.

Immediate loss of vision due to retinal pigment epithelial tear after anti-angiogenesis treatment of pigment epithelial detachment

Intravitreal injection of ranibizumab, an antivascular endothelial growth factor (VEGF) drug, is currently the primary treatment for wet age-related macular degeneration (AMD) in the UK. Use of ranibizumab for the treatment of isolated pigment epithelial detachments (PEDs) without the presence of an occult choroidal neovascular membrane has not been studied in a randomized controlled fashion and is strictly off-label. One possible complication of intravitreal injection of the drug is retinal pigment epithelial (RPE) tear. To date, the etiology of RPE tear associated with intravitreal injection is unknown; it could be attributed to rapid contraction of the neovascular membrane by fibrosis, perhaps triggered by the drug. We report a case of an RPE tear occurring less than a minute after intravitreal injection of ranibizumab for a fibrovascular PED. To our knowledge, this is the first report of such a case.

Spectral domain optical coherence tomography features of multiple subfoveal retinal pigment epithelial tears after intravitreal bevacizumab

Retinal pigment epithelial (RPE) tear has been described to occur spontaneously, after laser photocoagulation and in recent times, after intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. In the latter case, the rapid contraction of the choroidal vascular membrane underneath a serous RPE detachment is believed to be the underlying cause. Preservation of good visual acuity after the occurrence of RPE tear with continued use of intravitreal VEGF agents has been reported. In this case report, we describe the occurrence of multiple RPE tears with the use of intravitreal bevacizumab and also correlate the preservation of visual acuity with features seen on spectral domain optical coherence tomography.

Contraction of occult choroidal neovascular membrane and rupture of the retinal pigment following verteporfin and bevacizumab treatment

Contraction of occult choroidal neovascular membrane and rupture of the retinal pigment following verteporfin and bevacizumab treatment

Scattered Lamellar Microholes as a Complication of Epiretinal Membranes

The authors present two cases of an unusual pattern of the fundus corresponding to multiple “scattered lamellar microholes” located at the periphery of thick and contractile idiopathic epiretinal membranes. The retinal defects were documented with blue reflectance fundus photographs and three-dimensional spectral domain optical coherence tomography. They seem to correspond to multiple small areas of partial-thickness or lamellar disruptions of the retina. The authors suggest that the contraction of the epiretinal membrane may have caused tangential traction on the adjacent inner retina, creating disruptions in the internal limiting membrane and inner retina.

Role of tumour necrosis factor-α (TNFα) in the functional properties of hyalocytes

Background/aimTumour necrosis factor-α (TNFα) is an inflammatory cytokine that is upregulated in various vitreoretinal diseases including uveitis and diabetic retinopathy. Recently, our studies have indicated that hyalocytes contribute to the...