Friedrich E. Kruse

Bio: Friedrich E. Kruse is an academic researcher from University of Erlangen-Nuremberg. The author has contributed to research in topics: Cornea & Transplantation. The author has an hindex of 60, co-authored 278 publications receiving 10611 citations.

Inhibition of Hemangiogenesis and Lymphangiogenesis after Normal–Risk Corneal Transplantation by Neutralizing VEGF Promotes Graft Survival

Abstract: PURPOSE. To evaluate the occurrence and time course of hem-and lymphangiogenesis after normal-risk corneal transplantation in the mouse model and to test whether pharmacologic strategies inhibiting both processes improve long-term graft survival. METHODS. Normal-risk allogeneic (C57BL/6 to BALB/c) and syngeneic (BALB/c to BALB/c) corneal transplantations were performed and occurrence and time course of hem- and lymphangiogenesis after keratoplasty was observed, by using double immunofluorescence of corneal flatmounts (with CD31 as a panendothelial and LYVE-1 as a lymphatic vascular endothelium-specific marker). A molecular trap designed to eliminate VEGF-A (VEGF Trap R1R2 ; 12.5 mg/kg) was tested for its ability to inhibit both processes after keratoplasty and to promote long-term graft survival (intraperitoneal injections on the day of surgery and 3, 7, and 14 days later). RESULTS. No blood or lymph vessels were detectable immediately after normal-risk transplantation in either donor or host cornea, but hem- and lymphangiogenesis were clearly visible at day 3 after transplantation. Both vessel types reached donor tissue at 1 week after allografting and similarly after syngeneic grafting. Early postoperative trapping of VEGF-A significantly reduced both hem- and lymphangiogenesis and significantly improved long-term graft survival (78% vs. 40%; P < 0.05). CONCLUSIONS. There is concurrent, VEGF-A-dependent hem- and lymphangiogenesis after normal-risk keratoplasty within the preoperatively avascular recipient bed. Inhibition of hem- and lymphangiogenesis (afferent and efferent arm of an immune response) after normal-risk corneal transplantation improves long-term graft survival, establishing early postoperative hem-and lymphangiogenesis as novel risk factors for graft rejection even in low-risk eyes.

Bevacizumab as a Potent Inhibitor of Inflammatory Corneal Angiogenesis and Lymphangiogenesis

Abstract: PURPOSE. To analyze whether bevacizumab can inhibit inflammatory angiogenesis and lymphangiogenesis in the cornea. Bevacizumab (Avastin; Roche, Welwyn Garden City, UK) is a recombinant, humanized, monoclonal antibody against VEGF-A that has been approved by the U.S. Food and Drug Administration for the treatment of colon carcinomas. METHODS. The mouse model of suture-induced corneal neovascularization was used to assess the antihemangiogenic and antilymphangiogenic effect of bevacizumab by systemic and topical application. Corneal flatmounts were stained with LYVE-1 as a specific lymphatic vascular endothelial marker and CD31 as a pan-endothelial marker, and blood and lymph vascularized areas were analyzed morphometrically. The inhibitory effect of bevacizumab on lymphatic endothelial cells (LECs) was analyzed with a colorimetric (BrdU) proliferation ELISA. The binding ability of bevacizumab to murine VEGF-A was analyzed by Western blot, ELISA, and surface plasmon resonance. RESULTS. The systemic and topical applications of bevacizumab significantly inhibited the outgrowth of blood (P 0.006 and P 0.0001, respectively) and lymphatic (P 0.002 and P 0.0001, respectively) vessels. Inhibition of the proliferation of LECs was also significant (P 0.0001). Western blot analysis, ELISA, and the surface plasmon resonance assay showed that bevacizumab binds murine VEGF-A. CONCLUSIONS. Topical or systemic application of bevacizumab inhibits both inflammation-induced angiogenesis and lymphangiogenesis in the cornea. This finding suggests an important role of VEGF-A in corneal lymphangiogenesis. Bevacizumab may be useful in preventing immune rejections after penetrating keratoplasty or tumor metastasis via lymphatic vessels. (Invest Ophthalmol Vis Sci. 2007;48:2545‐2552) DOI:

A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty.

Abstract: Purpose Lamellar techniques for selective replacement of diseased corneal structures have recently been improved. Descemet membrane endothelial keratoplasty (DMEK) allows the sole replacement of the endothelium--Descemet membrane layer (EDM). However, wide-spread use of DMEK is currently limited because of problems with donor preparation namely the tearing of the Descemet membrane and the difficulty to unfold the EDM graft in the anterior chamber (AC). Methods A standardized DMEK procedure that allows safe preparation of EDM, atraumatic introduction of EDM into the AC, reliable orientation of EDM during surgery, and stepwise unfolding within the AC is described in 80 patients. Visual acuity and corneal endothelial cell density were assessed. Results A stepwise approach using a novel bimanual underwater technique to harvest EDM from donor corneal buttons allows reproducible generation of grafts without tearing the Descemet membrane. Injection of the EDM roll into the AC is achieved by use of a standard injector cartridge, whereas the depth of AC is maintained by an irrigation handpiece. Marks at the margin of EDM allow orientation. Finally, unfolding EDM in the AC is achieved by sequential use of water jets and air bubbles. In the early phase of the learning curve, 4 patients were regrafted because of graft failure. Endothelial cell density decreased from 2600 6 252 to 1526 6 341 cells per square millimeter 1 month after DMEK. Conclusions A novel technique for graft preparation and EDM injection results in improved safety with a high rate of successful DMEKs.

Engineered Nanoparticles for Drug Delivery in Cancer Therapy

Abstract: In medicine, nanotechnology has sparked a rapidly growing interest as it promises to solve a number of issues associated with conventional therapeutic agents, including their poor water solubility (at least, for most anticancer drugs), lack of targeting capability, nonspecific distribution, systemic toxicity, and low therapeutic index. Over the past several decades, remarkable progress has been made in the development and application of engineered nanoparticles to treat cancer more effectively. For example, therapeutic agents have been integrated with nanoparticles engineered with optimal sizes, shapes, and surface properties to increase their solubility, prolong their circulation half-life, improve their biodistribution, and reduce their immunogenicity. Nanoparticles and their payloads have also been favorably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect, and the spatial variations in the pH value. Additionally, targeting ligands (e.g., small organic molecules, peptides, antibodies, and nucleic acids) have been added to the surface of nanoparticles to specifically target cancerous cells through selective binding to the receptors overexpressed on their surface. Furthermore, it has been demonstrated that multiple types of therapeutic drugs and/or diagnostic agents (e.g., contrast agents) could be delivered through the same carrier to enable combination therapy with a potential to overcome multidrug resistance, and real-time readout on the treatment efficacy. It is anticipated that precisely engineered nanoparticles will emerge as the next-generation platform for cancer therapy and many other biomedical applications.

TFOS DEWS II Diagnostic Methodology report

Abstract: The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where DED is a comorbidity. Prior to diagnosis, it is important to exclude conditions that can mimic DED with the aid of triaging questions. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the conduct of diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin). Meibomian gland dysfunction, lipid thickness/dynamics and tear volume assessment and their severity allow sub-classification of DED (as predominantly evaporative or aqueous deficient) which informs the management of DED. Videos of these diagnostic and sub-classification techniques are available on the TFOS website. It is envisaged that the identification of the key tests to diagnose and monitor DED and its sub-classifications will inform future epidemiological studies and management clinical trials, improving comparability, and enabling identification of the sub-classification of DED in which different management strategies are most efficacious.

Integrins in angiogenesis and lymphangiogenesis

Abstract: Blood vessels promote tumour growth, and both blood and lymphatic vessels facilitate tumour metastasis by serving as conduits for the transport of tumour cells to new sites. Angiogenesis and lymphangiogenesis are regulated by integrins, which are members of a family of cell surface receptors whose ligands are extracellular matrix proteins and immunoglobulin superfamily molecules. Select integrins promote endothelial cell migration and survival during angiogenesis and lymphangiogenesis, whereas other integrins promote pro-angiogenic macrophage trafficking to tumours. Several integrin-targeted therapeutic agents are currently in clinical trials for cancer therapy. Here, we review the evidence implicating integrins as a family of fundamental regulators of angiogenesis and lymphangiogenesis.