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Gabriele E Lang

Publications and source records attributed to Gabriele E Lang.

At least 19 recordsLinked to original sources
PubMed2006

Effect of growth factors on proliferation and expression of growth factor receptors in a human lens epithelial cell line.

PURPOSE: To investigate the effect of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), and transforming growth factor beta 2 (TGFbeta2) on proliferation of a human lens epithelial cell line (HLEC-SRA 01/04); the effect of bFGF and TGFbeta2 on proliferation of human lens epithelial cells (HLECs); and the expression of bFGF, EGF, IGF-1, and TGFbeta2 receptors in an HLEC-SRA 01/04 cell line. SETTING: Department of Ophthalmology, University of Ulm, Ulm, Germany. METHODS: Both HLEC and HLEC-SRA 01/04 were treated with 1 to 50 ng/mL bFGF and TGFbeta2) Additionally, HLEC-SRA 01/04 were cultured with EGF and IGF-1 at a concentration of 1 to 50 ng/mL for 48 hours in the presence of [3H]-thymidine. In all experiments, untreated serum-free negative controls were used. (3H)-thymidine incorporation as a direct measure of lens epithelial cell proliferation was assessed by liquid scintillation counting. The expression of bFGF, EGF, IGF-1, and TGFbeta2 receptors in HLEC-SRA 01/04 were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was performed using the 2-sample t test for the means. RESULTS: Proliferation of HLECs was dose dependently induced by bFGF and TGFbeta2, showing maximum effects at 10 ng/mL (P = .0003) and at 50 ng/mL (P < .0001), respectively. Proliferation of HLEC-SRA 01/04 was also induced by bFGF, showing slight but significant effects (P < .03). Additionally, HLEC-SRA 01/04 proliferation was dose-dependently induced by EGF with a maximum effect at 5 ng/mL (P < .01), IGF-1 with a maximum effect at 5 ng/mL (P < .0001), and TGFbeta2 with a maximum effect at 10 ng/mL (P < .0001) compared with the control. The RT-PCR analysis revealed bFGF, EGF, IGF-1, and TGFbeta2 receptor expression in the HLEC-SRA 01/04 cell line. CONCLUSIONS: The data showed that bFGF and TGFbeta2 are strong mitogens for HLEC. The HLEC-SRA 01/04 cell line derived from HLEC reacted to growth factors, with cell proliferation only to a lesser extent. Such quiescence of these cells, when compared with cells in primary culture, cannot be explained by the lack of respective receptors for growth factors. Further investigation of growth factor-induced responses of both cell types will provide new insight into the proliferative processes involved in postoperative secondary cataract formation.

Cell Line↗
PubMed2006

TGFbeta induces transdifferentiation of iBREC to alphaSMA-expressing cells.

Transforming growth factor beta (TGFbeta) both inhibits proliferation of macrovascular endothelial cells and promotes their transdifferentiation to alpha-smooth-muscle-actin (alphaSMA)-expressing mesenchymal cells in vitro. Recently, we have confirmed that proliferation of immortalized bovine retinal microvascular endothelial cells (iBREC) is strongly inhibited by TGFbeta2. We now demonstrate a complete transition of both parental iBREC and single cell-derived subclones from cobblestone morphology to a ragged appearance as a consequence of incubation for a few days with 10 ng/ml TGFbeta1 or TGFbeta2. Depending on the type of culture medium, 5-40% of these cells strongly expressed alphaSMA after approximately 6 days whereas expression of the endothelial cell-specific marker proteins von Willebrand factor and VE Cadherin (CD144) declined. Expression of alphaSMA, associated with formation of stress fibers, was first detected in single cells and then spread to adjacent cells, and declined slowly after prolonged cultivation in medium without TGFbeta2. However, re-constitution of vWF expression was not observed. TGFbeta2-induced phenotypic alterations were specific, as they were not caused by treatment of iBREC with VEGF, IGF-1 or bFGF. Induction of alphaSMA expression but not effects on morphology was strongly inhibited by bFGF, whereas IGF-1 enhanced TGFbeta2-induced alphaSMA expression. These findings may have an important impact on the understanding of development of microvascular complications of diabetes such as diabetic retinopathy.

Actins↗
PubMed2005

Effect of extracellular matrix on proliferation and differentiation of porcine lens epithelial cells.

BACKGROUND: Proliferation and differentiation of lens epithelial cells (LECs) are important mechanisms of secondary cataract formation. After extracapsular cataract extraction the extracellular matrix (ECM) around the remaining LECs is altered compared with the intact lens. This study investigated the effects of different ECMs on cell proliferation and alpha-smooth muscle actin (alpha-SMA) expression, a marker for myofibroblasts, in cultured porcine LECs. METHODS: Porcine LECs were cultured for 3 days (cell proliferation assay) or 4 days (alpha-SMA expression) on wells and glass cover slips, respectively, coated with laminin, fibronectin, type I collagen or type IV collagen. LECs cultured on uncoated wells or cover slips served as control. Proliferative response was measured by [(3)H]-thymidine incorporation into DNA. alpha-SMA was detected immunocytochemically with a mouse monoclonal antibody, and the relative numbers of alpha-SMA-positive cells were calculated. Statistical analysis was performed using Student's unpaired t-test. RESULTS: Cell proliferation was significantly increased by coating with fibronectin (10,320.5+/-6,073 counts per minute; p<0.0001) (mean +/- SD), type I collagen (12,507.3+/-3,914.2 CPM; p<0.0001) and type IV collagen (9,591.4+/-4,088 CPM; p<0.0001) compared with control (1,876.5+/-998 CPM), whereas coating with laminin had no effect (1,760.8+/-812.6 CPM; p=0.7271). The ratio of alpha-SMA-positive LECs cultured on uncoated cover slips for a period of 4 days was 12.2+/-3.51%. This ratio was significantly increased by coating with fibronectin (24.3+/-4.56%; p=0.0001) and type I collagen (21.2+/-8.48%; p=0.0142). Coating with laminin (9.8+/-3.67%; p=0.1682) and type IV collagen (9.0+/-7.09 %; p=0.2491) slightly decreased alpha-SMA expression, but this effect was not statistically significant. CONCLUSIONS: Fibronectin and type I collagen stimulated both cell proliferation and alpha-SMA expression in cultured porcine LECs. Because fibronectin and type I collagen are not normally present in the adult lens, their possible introduction into the lens capsule after cataract surgery may play a critical role in the development of posterior capsule opacification.

Actins↗
PubMed2005

Octreotide inhibits growth factor-induced and basal proliferation of lens epithelial cells in vitro.

PURPOSE: To evaluate whether a synthetic analog of somatostatin, octreotide, has an inhibitory effect on lens epithelial cell (LEC) proliferation induced by basal and basic fibroblast growth factor as well as insulin-like growth factor 1. METHODS: Confluent LEC cultures were kept in serum-free defined medium containing [(3)H]-thymidine in the presence of octreotide alone at the concentration range of 10(-7) M to 10(-10) M or in combination with either basic fibroblast growth factor or insulin-like growth factor 1. Additionally, the expression of somatostatin receptors (1-5) in LECs were analyzed by reverse transcription-polymerase chain reaction. RESULTS: Octreotide decreased the proliferation of human LECs in a dose-dependent manner, exhibiting a maximal inhibitory concentration at 10(-9) M (P<.03). Moreover, octreotide (10(-9) M) potently inhibited basic fibroblast growth factor- and insulin-like growth factor 1-induced bovine lens epithelial cell proliferation (P<.0001). The respective products of all 5 subtypes of somatostatin receptors were found in human LECs and somatostatin receptor type 2 in bovine LECs. CONCLUSION: The data show that, depending on the concentration, octreotide is able to decrease proliferative responses of LECs. Moreover, the cell proliferation induced by growth factors was potently inhibited by octreotide. Therefore, octreotide could be a potential drug after cataract surgery in prevention of growth factor-dependent proliferative disorders such as posterior capsule opacification and anterior capsule contraction in diabetic patients.

Animals↗
PubMed2005

Generation and characterization of iBREC: novel hTERT-immortalized bovine retinal endothelial cells.

Primary retina-derived endothelial cells isolated from bovine and other animal tissues are extremely useful for studying the molecular mechanisms involved in the pathogenesis of diabetic retinopathy. Preparations of primary bovine retinal endothelial cells (BREC), however, usually contain a number of contaminating non-endothelial cells, e.g. pericytes which have been shown to inhibit proliferation of endothelial cells. To overcome this major drawback, we immortalized BREC by reconstitution of telomerase activity as a consequence of CMV promoter-driven expression of the catalytic domain of human telomerase. Immortal BREC (iBREC) have the capacity to proliferate for >90 passages over 10 months and constantly express endothelial marker proteins. In addition, iBREC behave like BREC with respect to stimulation of proliferation with VEGF, IGF-1 and bFGF, indicating that we have generated a stable endothelial cell line closely related to the corresponding primary cells.

Animals↗
PubMed2003

Adherence and viability of porcine lens epithelial cells on three different IOL materials in vitro.

BACKGROUND: The purpose of the study was to evaluate porcine lens epithelial cell (LEC) adhesion and viability on three different intraocular lens (IOL) materials. METHODS: The IOL materials tested were poly(methylmethacrylate) (PMMA), silicone and hydrophobic acrylate. Primary porcine LECs were cultured on four discs of each material over a period of 10 days and, additionally, on six discs of the hydrophobic acrylate over a period of 20 days. Cells grown on untreated wells of a 96-well microtiter plate served as a control. Cell adhesion was photodocumentated on days 1, 2, 3, 4, 6, 8, 10, 14,17 and 20. A cell viability test using the LIVE/DEAD kit (Molecular Probes) was carried out at the end of the investigation. Experiments were run in triplicate. Statistical analysis was performed using the Student's t-test. RESULTS: Confluent cell growth was reached on the hydrophobic acrylate discs and the control wells within 1 day and remained stable during the experiment. Only a few round cells were adherent on PMMA and silicone discs, and their number decreased during the experiment. After 10 days of culturing, the viability test (mean +/- SD) revealed 81.79 +/- 51.74% live cells on acrylate discs, which was not different from the control (105.83 +/- 21.78%, P=0.1589). Significantly lower relative numbers of live cells (P>0.0001) were found on PMMA (-0.62 +/- 2.24%) and silicone (21.47 +/- 8.42%) discs. The percentage of dead cells was significantly higher (P<0.0001) on hydrophobic acrylate discs (29.69 +/- 12.61%) compared to the control (-1.49 +/- 4.13%). After a culture period of 20 days, the percentage of live cells on hydrophobic acrylate discs (49.45 +/- 27.98%) was lower compared to day 10, but was not significantly different from control wells (58.77 +/- 10.71%) (P=0.2299). CONCLUSIONS: Significantly fewer cells grew on PMMA and silicone discs compared to the control. Confluent cell growth and numbers of viable cells comparable to the control were observed on hydrophobic acrylate discs after a culture period of 20 days with a significantly higher percentage of dead cells.

Animals↗
PubMed2003

[Evulsion of the optic nerve following blunt bulbar trauma. Case report and review of the literature].

BACKGROUND: Evulsion of the optic nerve is a rare form of traumatic optic neuropathy. It is a rupture of the optic nerve at the disc without damage of its sheaths occurring in association with a blunt skull trauma or a blunt bulbar trauma. METHOD: We report on a 13-year old girl with complete evulsion of the optic nerve after blunt bulbar trauma and give a literature review. RESULTS: While swinging on a liana the patient had crashed into a tree. The initial examination 3 hours after the accident revealed at the right eye an amaurosis without any afferent reaction of the pupil to light. Ophthalmoscopy displayed a vitreous haemorrhage at the optic disc, peripapillar white retina and interruption of the blood flow of all visible retinal vessels. Fluorescein angiogram showed no retinal perfusion and a detatched retina above the disc. Echographic examination revealed a vitreous haemorrhage at the disc shaped like a mushroom. From the eighth day, examination of the retina became impossible due to disseminating vitreous haemorrhage. After 8 months vitreous haemorrhage had disappeared revealing a white fibrosis at the area of the optic disc. Since first histological description of an optic nerve evulsion by His in 1856, 42 patients with complete and 23 with partial evulsion of the optic nerve were reported in the literature. In our review different mechanisms of injury are discussed. CONCLUSION: Evulsion of the optic nerve is rarely reported. It is possible that it may occur more frequently, because it cannot be seen in blunt or also penetrating bulbar traumas with severe intraocular cloudiness.

Adolescent↗
PubMed2003

[Recurrent corneal ulcer in a patient with Crohn's disease associated with epidermolysis bullosa acquisita].

BACKGROUND: Crohn's disease is a chronic inflammatory bowel disease, leading to ocular manifestations in 4 - 8 % of patients. We report on a patient with Crohn's disease, who developed in association with epidermolysis bullosa acquisita a progressive corneal ulcer. PATIENT: A 26-year old patient with a 3-year history of Crohn's disease presented with a peripheral corneal ulcer of the right eye. The anterior chamber was deep and quiet. Fundus examination was normal. Corneal smears displayed no bacterial growth. Visual acuity of the right eye was 20/25. Examination of the left eye was normal. Furthermore, he had developed cutaneous blisters on the arms and legs. Despite treatment with topical antibiotics and systemic immunosuppressive therapy with tacrolimus, azathioprine and methylprednisolone the corneal manifestation deteriorated. Therefore, an amniotic membrane was transplanted for treatment of the corneal ulcer; however, this was followed by melting of the amniotic membrane within a few days. Additional therapeutic procedures including further amniotic membrane transplantations and autologous conjunctival grafts have been performed. This was regularly unsuccessful. The corneal ulcer increased in size and extended into the sclera. Therefore a tectonic sclerokeratoplasty was necessary. Histologic examination of the excised corneoscleral tissue revealed an extensive stromal thinning associated with inflammatory infiltration of the cornea and sclera. CONCLUSIONS: Corneal complications in patients with Crohn's disease are very rare in contrast to conjunctivitis, episcleritis und uveitis. To the best of our knowledge, this is the first description of a patient with Crohn's disease and epidermolysis bullosa acquisita developing progressive corneal ulcer. How closely an assumed autoimmune mechanism in the cornea is related to Crohn's disease or epidermolysis bullosa acquisita, is not known.

Adult↗
PubMed2003

Phenotypic variability in three carriers from a family with choroideremia and a frameshift mutation 1388delCCinsG in the REP-1 gene.

PURPOSE: To perform genotype-phenotype correlations in a family with choroideremia. METHODS: A three-generation family with two affected males and five carriers was the subject of the study. Molecular genetic analysis using single-strand conformation polymorphism analysis (SSCP) was conducted in all subjects, while electroretinography (ERG), multifocal ERG (mfERG), scanning laser ophthalmoscope microperimetry (SLO perimetry), fluorescein angiography, and Arden contrast color testing were performed in one male and three carriers. RESULTS: The findings in the affected male were typical for advanced choroideremia. The three carriers demonstrated a variable clinical phenotype including reduction of visual acuity and ERG and angiographic changes in one. Molecular genetic analysis revealed a functional null mutation (1388delCCinsG) in the REP-1 gene. CONCLUSIONS: A severe retinal pathology was found in the affected male, indicating that the 1388delCCinsG is a severe mutation. Varying phenotypes were present in the three carriers examined. The phenotype in carriers has been explained by random X-inactivation with varying expression of the inactivated and activated gene copy inside the same cell of both the retinal pigment epithelium and the rods. This thesis is in agreement with the clinical data obtained here.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Octreotide inhibits growth factor-induced bovine choriocapillary endothelial cells in vitro.

BACKGROUND: Response to growth factors by the choriocapillaris is one of the main aspects in the development and progression of choroidal neovascularization in age-related macular degeneration (AMD). The aim of the study was to examine the effect of octreotide--an analogue of somatostatin with possible favorable effects in the treatment of age-related macular degeneration--on growth factor-activated bovine choriocapillary endothelial cells (BCEC). METHODS: Cultivated BCEC were stimulated with 20 ng/ml VEGF, 5 ng/ml bFGF, 50 ng/ml TGFbeta(2), or 50 ng/ml IGF-I for 24 h. Afterwards, the cells were incubated for a further 24 h with octreotide (10(-6) M). BCEC proliferation was determined by [(3)H]-thymidine incorporation. The experiments were performed in normal conditions and in O(2)-limited (5% O(2)) atmosphere. RESULTS: VEGF, bFGF, and IGF-I significantly stimulated BCEC proliferation under normoxic as well as under hypoxic conditions ( P<0.05); the value for TGFbeta(2)stimulation was not significant. Under normoxic conditions, after addition of octreotide to VEGF-, bFGF-, and IGF-I-stimulated cells there was no longer any significant [(3)H]-thymidine incorporation compared to the control medium. Under hypoxic conditions similar results were obtained after addition of octreotide to VEGF-, bFGF-, and IGF-I-stimulated cells. CONCLUSION: Octreotide has inhibitory properties after activation of BCEC with growth factors under normoxic and hypoxic conditions in vitro. Since activation of these cells is a crucial event in the development and progression of AMD, octreotide may be a potential drug for treatment of choroidal neovascularization in these patients.

Animals↗
PubMed2002

Morphometric changes of the choriocapillaris and the choroidal vasculature in eyes with advanced glaucomatous changes.

PURPOSE: In addition to an elevated intraocular pressure a compromise of the ocular blood supply have been implicated in the pathogenesis of primary open-angle glaucoma. The purpose of this study was to quantify morphologic changes in the choroid including choriocapillaris thickness and density and diameter of large choroidal vessels in post mortem eyes with advanced primary open-angle glaucoma. METHODS: We analyzed 20 eye bank eyes (provided from the Georgia Eye Bank in Atlanta) with end stage primary open-angle glaucoma and compared them with 20 age-matched control eye bank eyes. The eyes were processed for light microscopy and following variables were measured with a digital filar micrometer: density and diameter of large choroidal vessels in the macular and equatorial choroid; thickness of the choroid in the macular and equatorial region; density and thickness of choriocapillaris in the macular, peripapillary, and equatorial choroid; and peripapillary capillary-free area nasal and temporal to the optic disk. RESULTS: Eyes with glaucoma displayed a lower density of the capillaries of the choriocapillaris as compared to control eyes in the macular, temporal peripapillary, and equatorial choroid with 0.50-0.55 (p=0.018), 0.46-0.51 (p=0.016), and 0.50-0.55 (p=0.038), respectively. There was no significant difference for the choriocapillaris density in the nasal peripapillary choroid, the thickness of the capillaries of the choriocapillaris in all assessed locations, and the nasal and temporal peripapillary capillary-free zone of the choriocapillaris between eyes with glaucomatous damage and controls. Assessment of large choroidal vessels in the macular choroid showed that eyes with glaucoma had a decreased density of veins (11.7-38.9 mm(-2); p<0.001) and arteries (7.7-12.4 mm(-2); p=0.005) and arteries with a higher diameter (45.6-28.2 microm; p<0.001) as compared to control eyes. The large vessels in the equatorial choroid displayed no significant difference in diameter but a lower density (21.2-44.1 mm(-2); p=0.017) in eyes with glaucomatous damage as compared to controls. CONCLUSION: Eyes with advanced glaucomatous damage after long standing primary open-angle glaucoma exhibit several changes including decreased density of capillaries of the choriocapillaris and decreased density of large choroidal vessels. We cannot conclude from our study whether the observed vascular changes in the choroid are primary pathogenic factors or secondary phenomena.

Aged↗
PubMed2002

[The role of protein kinase C in the pathophysiology of diabetic retinopathy].

Hyperglycemic control in diabetes mellitus is a major key to prevent the development and progression of diabetic retinopathy. One important pathomechanism in the development of diabetic complications is the activation of protein kinase C (PKC) induced by high glucose due to an increased diacylglycerol (DAG) level. Resulting vascular dysfunctions are increased vascular permeability and contractility, increased production of extracellular matrix and cell proliferation. The PKC isoenzyme family plays a fundamental role in the cellular signal transduction via phosphorylation and modification of enzymes, receptors, transcription factors and kinases. The PKC activation influences the gene transcription and ion transport. Different PKC isoenzymes function as mediators but also as inhibitors of the insulin effects. The hyperglycemia induced DAG production seems to predominantly activate PKC-beta in retinal vascular endothelial cells. The development of selective PKC-beta inhibitors enables new pharmacological therapeutical approaches for treatment of diabetic retinopathy. Ongoing clinical studies investigate if the treatment with specific PKC-beta inhibitors can prevent the progression of diabetic retinopathy and diabetic macular edema.

Blood Glucose↗
PubMedDate not supplied

[Ophthalmia nodosa caused by the hairs of the bird spider (family Theraphosidae) or hairy megalomorph (known in the US as tarantula)--case report and review of the literature].

BACKGROUND: Bird spiders, known in the US as tarantulas, are large hairy spiders that have become increasingly popular as pets in the Western world. We present a patient with a red irritated eye from exposure to the hairs of a spider of the Theraphosidae family, and review the literature. PATIENT AND METHODS: We report on a 28-year old patient who was referred to our clinic with a red irritated eye following playing with a Chilean rose-haired bird spider (known in the US as tarantula). In addition, we reviewed the literature concerning similar cases using the Medline database and cited literature in the retrieved articles. RESULTS: Our patient displayed theraphosidae (tarantula) hairs in the cornea of the right eye and developed a uveitis and a retinochoroiditis with associated vitritis. Treatment with topical corticosteroids resulted in an improvement of signs and symptoms, although the improvement was slow and incomplete. The disease process consists of a granulomatous reaction to the spider hairs. Hairs of Theraphosidae spiders (tarantulas) may cause inflammation at all levels of the eye, from the conjunctiva to retina. We were able to identify 14 cases of Ophthalmia nodosa secondary to the exposure to the tarantula hairs in the literature. Therapy includes removal of the offending hairs when possible and topical treatment with steroids. CONCLUSION: Although the large hairy bird spiders (tarantulas) are considered harmless pets, ophthalmia nodosa is a potential danger when handling them. Ophthalmia nodosa has an unknown prognosis and may be difficult to manage.

Adult↗