Femtosecond laser-assisted repeat keratoplasty: a case series.

Purpose: To evaluate the feasibility of femtosecond laser-assisted repeat penetrating keratoplasty (PK) in eyes having undergone corneal graft, thus presenting intracorneal scar tissue.

Method: Repeat PK was performed with femtosecond laser (Intralase FS TM System; Abbott Medical Optics, Inc, Santa Ana, CA) creating a "top-hat" or "mushroom" configuration.

Results: Four patients were included in this study.

Predicting the risk for corneal graft rejection by aqueous humor analysis.

Purpose: Cytokine patterns determined in the aqueous humor before penetrating keratoplasty (PK) may enable us to predict immune reactions (IR). We therefore analyzed 6 cytokines in the aqueous humor of patients before PK. By prospective clinical follow-up, we tested whether patients who developed an IR would present different preoperative cytokine patterns compared to patients without IR.

Radioprotective gene therapy.

Introduction: Radiation-induced myelosuppression or mucositis can limit the effectiveness of radiotherapy by requiring dose reduction or delaying treatment of tumour patients. The transfer of a radioprotective gene into normal tissue cells would provide the opportunity to reduce the risks associated with haematopoietic or intestinal toxicity after irradiation.

Areas Covered: Several potentially radioprotective genes like multidrug resistance 1 (MDR1), snail homolog 2 (SNAI2), and superoxide dismutases have been evaluated in preclinical models for their radioprotective potential in the last years.

Distinct role of endocytosis for Smad and non-Smad TGF-β signaling regulation in hepatocytes.

Background & Aims: In injured liver, TGF-β affects all hepatic cell types and participates in wound healing and fibrogenesis. TGF-β downstream signaling is highly complex and cell type dependent, involving Smad and non-Smad signaling cascades thus requiring tight regulation. Endocytosis has gained relevance as important mechanism to control signaling initiation and termination.

Operational post-keratopasty graft tolerance due to differential HLAMatchmaker matching.

Purpose: Penetrating keratoplasty can restore vision in corneal blindness. However, immunologic rejection threatens graft survival. Matching donors at swine leukocyte antigen (SLA)-class II convey allo-specific tolerance in a large animal kidney-transplantation model despite mismatches at SLA-class I.

Retroviral vectors for gene therapy.

Since their first clinical trial 20 years ago, retroviral (gretroviral and lentiviral) vectors have now been used in more than 350 gene-therapy studies. Retroviral vectors are particularly suited for gene-correction of cells due to long-term and stable expression of the transferred transgene(s), and also because little effort is required for their cloning and production. Several monogenic inherited diseases, mostly immunodeficiencies, can now be successfully treated.

Unrestricted somatic stem cells: interaction with CD34+ cells in vitro and in vivo, expression of homing genes and exclusion of tumorigenic potential.

Background Aims: Transplantation of allogeneic hematopoietic stem cells (HSC) within the framework of hematologic oncology or inherited diseases may be associated with complications such as engraftment failure and long-term pancytopenia. HSC engraftment can be improved, for example by co-transplantation with mesenchymal stem cells (MSC). Recently, a new multipotent MSC line from umbilical cord blood, unrestricted somatic stem cells (USSC), has been described.

Sustained glutamate receptor activation down-regulates GABAB receptors by shifting the balance from recycling to lysosomal degradation.

Metabotropic GABA(B) receptors are abundantly expressed at glutamatergic synapses where they control excitability of the synapse. Here, we tested the hypothesis that glutamatergic neurotransmission may regulate GABA(B) receptors. We found that application of glutamate to cultured cortical neurons led to rapid down-regulation of GABA(B) receptors via lysosomal degradation.

Long-term graft survival in penetrating keratoplasty: the biexponential model of chronic endothelial cell loss revisited.

Aim: To present a novel interpretation of the biexponential nature of chronic endothelial cell loss after penetrating keratoplasty (PK). We hypothesize that the fast component of endothelial cell loss reflects the endothelial cells of graft origin. The slow component might just reflect cell loss of the recipient endothelium.

[Therapeutic applications of the femtosecond laser in corneal surgery].

Since 2001 the femtosecond laser has primarily been used in refractive surgery, e. g., for lasik, implantation of intracorneal ring segments or antiastigmatic corneal incisions.

SNAI2 as a novel radioprotector of normal tissue by gene transfer using a lentiviral bicistronic SIN vector.

Tumor radiotherapy with large-field irradiation results in an increase of p53-dependent apoptosis of the radiosensitive hematopoietic stem cells. Proapoptotic PUMA is a transcriptional target of p53. Thus suppression of PUMA expression by gene therapy with the transcription repressor SNAI2 as transgene might be a potential approach for normal tissue protection during radiotherapy.

Good manufacturing practice-grade production of unrestricted somatic stem cell from fresh cord blood.

Background Aims: The discovery of unrestricted somatic stem cells (USSC), a non-hematopoietic stem cell population, brought cord blood (CB) to the attention of regenerative medicine for defining more protocols for non-hematopoietic indications. We demonstrate that a reliable and reproducible method for good manufacturing practice (GMP)-conforming generation of USSC is possible that fulfils safety requirements as well as criteria for clinical applications, such as adherence of strict regulations on cell isolation and expansion.

Methods: In order to maintain GMP conformity, the automated cell processing system Sepax (Biosafe) was implemented for mononucleated cell (MNC) separation from fresh CB.

Analysis of self-inactivating lentiviral vector integration sites and flanking gene expression in human peripheral blood progenitor cells after alkylator chemotherapy.

Abstract Hematotoxicity is a major and frequently dose-limiting side effect of chemotherapy. Retroviral methylguanine-DNA-methyltransferase (MGMT; EC 2.1.

Overexpression of caveolin-1 in lymphoblastoid TK6 cells enhances proliferation after irradiation with clinically relevant doses.

Background And Purpose: The transmembrane protein caveolin-1 (CAV1) is an essential component of caveolae, small membrane invaginations involved in vesicle formation. CAV1 plays a role in signal transduction, tumor suppression and oncogene transformation. Previous studies with CAV1 knockout mice and CAV1 knockdown in pancreatic tumor cells implicated CAV1 in mediating radioresistance.

Distinct cytokine pattern in aqueous humor during immune reactions following penetrating keratoplasty.

Purpose: Cytokine patterns in the aqueous humor before penetrating keratoplasty might permit us to predict the development of immune reactions. We therefore analyzed ten different cytokines in the aqueous humor of patients before and following penetrating keratoplasty.

Methods: We collected aqueous humor from patients undergoing cataract extraction or penetrating keratoplasty (baseline, n=197), from patients undergoing cataract extraction after penetrating keratoplasty without signs of an endothelial immune reaction (acceptors, n=33), and from patients who underwent irrigation of the anterior chamber due to endothelial immune reactions (rejectors, n=25).

[Femtosecond laser-assisted penetrating keratoplasty].

The femtosecond laser technique allows completely new trephination methods in penetrating keratoplasty with profiles in the graft and the host cornea. The most common so-called profiled trephinations are the top hat and mushroom profiles. Due to the profile it is easier to get a watertight wound closure intraoperatively and due to the larger wound surface the wound healing is faster and more stable.

Chemoprotection of human hematopoietic stem cells by simultaneous lentiviral overexpression of multidrug resistance 1 and O(6)-methylguanine-DNA methyltransferase(P140K).

Myelotoxicity is a dose-limiting effect of many chemotherapeutic regimens. Thus, there is great interest in protecting human hematopoietic stem cells by the transfer of drug resistance genes. The main focus of this study was the simultaneous overexpression of multidrug resistance 1 (MDR1) and the O(6)-benzylguanine (O(6)-BG)-resistant mutant MGMT(P140K) (O(6)-methylguanine-DNA methyltransferase) with a bicistronic lentiviral vector (HR'SIN-MDR1-IRES-MGMT(P140K)), with regard to the capability to convey chemoprotection in the leukemia cell line, HL60, and human hematopoietic stem cells (CD34(+)).

[Keratoplasty: laminate or penetrate? Part 1: penetrating keratoplasty].

A number of corneal disorders sooner or later call for a decision as to whether corneal grafting is necessary. The problems of the current gold standard treatment, conventional penetrating keratoplasty (PKP), have yet to be fully solved, namely accelerated postoperative endothelial cell loss, endothelial immune reactions and the induction of astigmatism, which depends among other things on the trephination technique used. The use of a hand trephine may lead to different cutting angles between donor and recipient, resulting in increased postoperative astigmatism.

[Keratoplasty: laminate or penetrate? Part 2: lamellar keratoplasty].

A number of corneal disorders sooner or later call for a decision as to whether corneal grafting is necessary. In contrast to the current gold standard, penetrating keratoplasty (PKP), former lamellar techniques had the disadvantage of worse visual outcomes due to interface problems. A number of recent new technical developments have led to a 'renaissance' of various lamellar keratoplasty methods.

Costs and financing. A cost calculation of an up-to-date eye bank in Germany.

Purpose: To estimate the averaged cost of processing a corneal graft for keratoplasty.

Methods: We estimated the total running costs of a German corneal bank for one year. All procurement-related expenses were calculated on the basis of 300 donors per year and a disavowal percentage of 50%.

[Isolated corneal intraepithelial dysplasia].

We present the case of an 83-year-old patient with an isolated epithelial dysplasia of the cornea. After corneal abrasion the lesion reoccurred 14 days later. The abrasion was then increased to cover the whole corneal epithelium and adjacent limbal and conjunctival areas were also biopsied.

[Procedural guidelines. Good tissue practice for cornea banks].

A cornea bank must have an organizational structure in which responsibility and authority to issue directives are clearly defined. It must also use a documented quality management system on the basis of good practice procedures which is maintained to the current standards. The personnel of a cornea bank must be present in sufficient numbers and be suitably qualified.

Toxic anterior segment syndrome following penetrating keratoplasty.

Objectives: To describe an outbreak of toxic anterior segment syndrome (TASS) following penetrating keratoplasty (PK) and to examine its possible causes.

Methods: Owing to a series of TASS following PK between June 6, 2007, and October 2, 2007, we reviewed the records of all patients who had undergone PK during that time. In addition to routine microbial tests on organ culture media, we looked for specific pathogens and endotoxins in all of the materials used for organ culture or PK.