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Biomedical subjects

F E Kruse

Publications and source records attributed to F E Kruse.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Multilayer amniotic membrane transplantation for corneal ulcers not treatable by conventional therapy - a prospective study of the status of cornea and graft during follow-up].

PURPOSE: The purpose of this prospective clinical study was to evaluate the condition of the cornea (epithelium and vascularization) and the membrane presence and retraction during follow-up after amniotic membrane transplantation in patients with persistent corneal ulcers. PATIENTS AND METHODS: Between June 1999 and November 2000 AM transplantation was performed in 30 consecutive patients (average age 59 +/- 17 years) with corneal ulcers refractory to clinical treatment. We evaluated the clinical diagnosis, localisation, size and depth of the ulcers, condition of the ocular surface and visual acuity before and after surgery. After complete removal of the epithelium and pannus, one (n=11), two (n=17) or three (n=2) layers of amniotic membrane were fixed with multiple interrupted sutures, depending on the depth of the lesion. A therapeutic contact lens was applied in most eyes and removed after one month. The most frequent diagnoses were chemical burn (5 x lime, 1 x lye and 1 x liquid aluminium), 7 x herpes, 3 x polyarthritis and 3 x blepharo-keratoconjunctivitis in neurodermitis. The ulcers had a medium length of 4.9 +/- 3.2 mm, a width of 3.5 +/- 3.0 mm and a depth ranging between 30 % and 95 % (68 +/- 21 %). RESULTS: Complete epithelial closure was achieved in 27 of 30 eyes (90 %). In 4 eyes a recurrent epithelial defect occurred after initial closure. At the 1-, 3- and 6 month follow-up the amniotic membrane was present in 93 %, 73 % or 30 %, respectively, but was more or less retractet in 52 %, 58 % or 67 %, respectively. A complete corneal epithelium was noted in 79 %, 89 % or 90 % of eyes, respectively. However, corneal neovascularization was observed in 24 %, 58 % or 60 % of eyes. Visual acuity was </= 20/400 in 60 % eyes preoperatively, but in 69 % after 3 months and in 78 % after 6 months of follow-up. CONCLUSION: In persistent corneal ulcers, amniotic membrane transplantation should be considered in early stages to achieve permanent epithelial closure in a less inflamed eye thus avoiding penetrating keratoplasty à chaud or conjunctival flaps. However, in eyes with broad descemetocele especially following chemical burns, this treatment modality does not seem to be effective.

Adult↗
PubMed2001

[Autologous serum for otherwise therapy resistant corneal epithelial defects - Prospective report on the first 70 eyes].

PURPOSE: The purpose of this prospective clinical pilot study was to evaluate the efficiency, practicability and safety of topical autologous serum for therapy resistant corneal epithelial defects. METHODS: Between November 1999 and June 2001 autologous serum therapy was applied in 70 eyes of 67 consecutive patients (age 18 to 92 [average 59 +/- 18] years) with corneal epithelial defects refractory to standard clinical treatment at the Department of Ophthalmology University Erlangen-Nürnberg. We evaluated localization, size of the defect, time until epithelial wound closure and the incidence of recurrences in relation to the clinical diagnosis. The blood was obtained by venipuncture, centrifuged and the non-diluted serum was filled in sterile bottles, kept in the + 4 (o)C refrigerator and hourly applied during daytime. Simultaneous systemic and topical medication depended on the underlying disease. RESULTS: In 45 eyes corneal epithelial defects appeared after penetrating keratoplasty but in 25 eyes corneal epithelial defects were not related to a corneal transplant. The epithelial defect had a medium length of 4.2 +/- 2.4 mm and a width of 3.0 +/- 1.8 mm. Previously, the patients had been treated with maximal topical therapy (including hyaluronic acid) for 13 +/- 11 days. Treatment with autologous serum lasted from 4 to 45 (mean 16 +/- 11) days. A complete corneal re-epithelialization was achieved in 57 of 70 eyes (81 %) after 3 to 45 (mean 15 +/- 12) days. Forty-eight of these 57 eyes (84 %) had no recurrence during a follow-up of 12 +/- 4 months. In 9 eyes (16 %) a recurrent epithelial defect occurred one or two months after initial closure. These eyes were treated successfully with a second autologous serum therapy (6 x), amniotic membrane transplantation (2 x) or repeat keratoplasty (1 x). Thirteen eyes (19 %) without primary success of autologous serum applied for 11 to 50 days were finally treated successfully with amniotic membrane transplantation (10 x) or repeat keratoplasty (3 x). CONCLUSION: In persistent corneal epithelium defects, autologous serum therapy can be considered as an effective and practicable therapy without adverse reactions. Especially in eyes after complicated penetrating keratoplasty the prognosis may be improved and more invasive treatment modalities such as botulinum toxin injection, amniotic membrane transplantation or (repeat) penetrating keratoplasty may be avoided. Definitive determinants for the success of this novel therapy have not been identified, yet. However, eyes with accompanying deep stromal defects do not seem to be good candidates.

Adolescent↗
PubMed2001

Glial cell-derived neurotrophic factor (GDNF)-induced migration and signal transduction in corneal epithelial cells.

PURPOSE: To identify signal-transduction pathways induced by glial cell-derived neurotrophic factor (GDNF) in corneal epithelial cells and to characterize its effect on cell migration. METHODS: Expression of GDNF receptor (GFR) alpha-1 in human corneal epithelium was detected by RT-PCR and Western blot analysis. Expression and phosphorylation of Ret, activation of focal adhesion kinase (FAK) and mitogen-associated protein kinase (MAPK) signaling pathways, and phosphorylation of paxillin by GDNF were investigated by immunoprecipitation and Western blot analysis in primary human corneal epithelial cells and a corneal epithelial cell line. The tyrosine kinase inhibitor herbimycin A and Ras farnesyltransferase inhibitor manumycin were used to specifically inhibit GDNF-induced signaling pathways. In vitro wound-healing assays and modified Boyden chamber analysis were performed to investigate the effect of GDNF on epithelial cell migration. RESULTS: Expression of GFRalpha-1 was detected in normal and transformed human corneal epithelium. GDNF induced tyrosine phosphorylation of Ret. Furthermore, tyrosine phosphorylation of FAK and phosphotyrosine kinase (Pyk) 2; serine phosphorylation of c-Raf, MEK1, and Elk 1; and tyrosine-threonine phosphorylation of Erk-1 and -2 were time-dependently activated in the presence of GDNF. Tyrosine phosphorylation of paxillin was also induced by GDNF. Migration of corneal epithelial cells was significantly stimulated by GDNF. Herbimycin A strongly inhibited the activation of Ret, FAK, c-Raf, and Erk-1 and -2; the phosphorylation of paxillin; and corneal epithelial cell migration. More specifically, the Ras inhibitor manumycin inhibited phosphorylation of c-Raf, MEK 1, Erk-1 and -2, and Elk 1, but not that of FAK. CONCLUSIONS: Corneal epithelial cells express receptors specific for GDNF that are used by GDNF to induce intracellular signaling. FAK and MAPK pathways seem to be activated by GDNF to modulate gene transcription and cell migration. FAK seems to be an upstream regulator of the MAPK cascade for GDNF signal transduction. As an inducer of FAK-dependent corneal epithelial migration, GDNF may play an important role in corneal regeneration and wound healing.

Blotting, Western↗
PubMed2000

Treatment of corneal neovascularization with dietary isoflavonoids and flavonoids.

The purpose of this study was to investigate the use of dietary isoflavonoids and flavonoids for the treatment of ocular neovascularization. Corneal blood vessels were induced by intrastromal implantation of pellets containing bFGF. Isoflavonoids and flavonoids (Genistein, Fisetin and Luteolin) were dissolved in a microemulsion to increase bioavailability and applied topically in concentrations between 0.5 and 1 ng ml(-1). Corneal neovascularization was quantified under the microscope. In comparison to control eyes, all three substances significantly inhibited corneal neovascularization (P < or = 0.05). Fisetin had the strongest effect followed by Genistein and Luteolin. No significant topical side effects were observed. We concluded that the isoflavonoid Genistein and two structurally related flavonoids are potent inhibitors of corneal angiogenesis in vivo. The wide distribution of the flavonoids in the plant kingdom together with the presented results suggests that flavonoids may contribute to the preventive effect of a plant-based diet on neovascular disease of the eye.

Administration, Topical↗
PubMed2000

[Ab interno trabeculectomy with the Nd:YLF picosecond laser].

BACKGROUND: The outcome of glaucoma surgery is limited by scar formation. As an alternative to current techniques, the opening of the trabecular meshwork ab interno may lead to increased outflow. This study examined the Nd:YLF picosecond laser for ab interno ablation of the trabecular meshwork without opening of the eye. PATIENTS AND METHODS: A Nd:YLF picosecond laser was used which allows tissue to be ablated even through fluids. We performed ablation with different spot sizes and energies in postmortem eyes. Afterwards the effect of the laser treatment was examined by electron microscopy. RESULTS: The ablation threshold for the cornea was found to be 20 J/cm2 for a pulse width of 30 ps. At a lower level of energy (10 J/cm2) ablation of the trabecular meshwork was possible. The size of the focus which was limited by the optics of the slit-lamp was about 50 microns. CONCLUSION: These initial results with a Nd:YLF picosecond laser confirm the possibility of ablating tissue in the trabecular meshwork ab interno without the need to open the eye.

Animals↗
PubMed2000

Cryopreserved human amniotic membrane for ocular surface reconstruction.

BACKGROUND: Amniotic membrane transplantation is used for the reconstruction of the ocular surface in the context of, for example, corneal ulcers or conjunctival scarring. The mechanisms by which preserved amniotic membrane grafts promote reepithelialization are unknown. As a first step the viability and proliferative capacity of amnion cells following cryopreservation of membranes in glycerol is investigated. METHODS: Fresh and cryopreserved (in 50% glycerol) amniotic membranes were investigated histologically and by vital stains. Following enzymatic digestion, amniotic cells were stained for viability and cultured in DMEM+10% FBS. In addition, explant cultures were established from fresh and cryopreserved membranes. RESULTS: Histological examination showed no significant morphological alteration following cryopreservation. While fresh membranes contained predominantly vital cells, no such cells were detected following cryopreservation. Also, cells removed enzymatically from cryopreserved membranes were not viable and did not grow in culture. While both epithelial and fibroblastic cells grew from fresh membranes, no growth was seen from cryopreserved membranes. CONCLUSION: The results suggest that the technique for preservation which is most widely used for ophthalmological amniotic membrane transplantation significantly impairs viability and proliferative capacity. This supports the clinical finding that neither immunological reactions nor signs of ingrowth of amniotic cells are observed in patients. Furthermore amniotic membrane grafts seem to function primarily as matrix and not by virtue of transplanted functional cells.

Amnion↗
PubMed2000

Scanning laser ophthalmoscope fundus perimetry before and after laser photocoagulation for clinically significant diabetic macular edema.

PURPOSE: To prospectively evaluate functional and funduscopic changes after laser treatment in patients with diabetic retinopathy and clinically significant macular edema by scanning laser ophthalmoscope fundus perimetry. METHODS: Thirty eyes of 30 patients with clinically significant macular edema as a result of diabetic retinopathy were prospectively examined before and at least 3 months after focal laser treatment with automatic fundus threshold perimetry using the scanning laser ophthalmoscope. Thresholds of light sensitivity were compared with age-corrected normal values and correlated with corrected visual acuity and subjective appraisal of visual function. RESULTS: In 30 eyes, fundus perimetry lasted for 10.5+/-2.7 (mean+/-SD) minutes with 322+/-67 stimulus presentations for each eye. Whereas eight eyes remained stable (< +/-1 dB change), 15 improved concerning mean deviation (MD) (3.1+/-1.7 dB) after focal laser treatment. Stability of fixation remained the same after focal laser treatment (0.75+/-0.57 degree). Laser scars showed marked loss of function (MD > 13 dB). CONCLUSIONS: Although light sensitivity was reduced in areas of macular edema, there was no correlation between the amount of edema and visual function. Fundus perimetry allows the creation of exact maps of retinal dysfunction before and after laser treatment. It may help in making management decisions in diabetic and nondiabetic patients by offering a sensitive parameter in addition to visual acuity.

Adult↗
PubMed2000

Neurotrophic factors in the human cornea.

PURPOSE: To investigate neurotrophic growth factors and corresponding receptors in human and rabbit corneal epithelium and stroma. METHODS: Transcription of nerve growth factor (NGF), neurotrophin 3 (NT-3), NT-4, brain-derived neurotrophic factor (BDNF), glial cell line- derived neurotrophic factor (GDNF), and receptors Trk A-E, was investigated by reverse transcription-polymerase chain reaction. DNA dot blot analysis allowed to estimate transcription levels. Single cell proliferation assays were performed using recombinant NGF, BDNF, and GDNF. Mitogen-activated protein kinase signal transduction was investigated with Western blot analysis using antibodies against activated and total extracellular signal-regulated kinase (ERK) 1/2 and the jun N-terminal protein kinase (JNK) 1/2. RESULTS: Transcription of NGF, NT-3, BDNF, and Trk A, Trk B, Trk C, and Trk E receptors was detected in both ex vivo and cultured epithelium and stroma. Transcription of NT-4 was only detected in epithelium and transcription of GDNF only in stroma. Levels of transcription were higher for NT-3, NT-4, and the Trk receptors and lower for NGF, BDNF, and GDNF. NGF and GDNF stimulated both epithelial colony formation and proliferation, whereas BDNF only enhanced colony formation. Stromal proliferation was enhanced in serum-free medium. In epithelium, predominantly ERK 1 was activated by NGF, GDNF, and BDNF. In stromal cells NGF and GDNF stimulated phosphorylation of ERK 1 and JNK 1. CONCLUSIONS: Neurotrophic factors and tyrosine kinase receptors are transcribed in the human cornea. GDNF and NGF stimulate corneal epithelial proliferation, and the effect of the latter might be mediated by activation of ERK 1. Neurotrophic factors have very specific effects on phosphorylation of ERK and JNK in epithelial and stromal cells. The differential expression of NT-4 and GDNF suggests a regulatory function within the cytokine network of the cornea.

Animals↗
PubMed1999

[Experimental external irradiation of corneal neovascularization].

UNLABELLED: The clinical effect of ionidizing radiation on ocular neovascularizations is controversial not only because of the variety of treatment modalities. The aim of our study was to investigate an experimental model which allows to evaluate radiation parameters and to study the mechanism of the inhibitory effect on neoangiogenesis. METHODS: Corneal angiogenesis was induced by use of a micropocket assay in NZW rabbits. Pellets with 500 ng bFGF in 2% methylecellulose were implanted into the stroma 2.0 mm from the limbus. Initiation of vessel growth occurred on day 3. At this time radiation was performed with different doses (single dose of 15 to 30 Gy or fractionated 5 x 5 Gy) using a 6 MeV linear accelerator. Vascular growth was quantified. RESULTS: Irradiation with a total dose of 25 Gy applied in a fractionated regimen or as single-dose irradiation on the day of surgery or on day 6 after surgery did not significantly reduce neovascular growth. In contrast, postoperative radiation therapy on day 3 was able to reduce the area of ingrowing vessels significantly (P < 0.01). In spite of the relatively high dose there were no significant side effects during the observation period of 8 weeks. CONCLUSION: Our results show that single-dose radiation (> or = 25 Gy) is sufficient to inhibit the growth of corneal neovascularizations. With this model it might be possible to investigate parameters for therapy of ocular neovascularizations as well as the underlying mechanisms.

Animals↗
PubMed1999

[Techniques for reconstruction of the corneal surface by transplantation of preserved human amniotic membrane].

Persistent defects of the ocular surface remain a therapeutic challenge, which often requires surgical intervention. Recently, transplantation of human amniotic membrane has been suggested for reconstruction of the corneal surface. We describe two techniques using cryo-preserved amniotic membrane. Transplantation of several layers of amniotic membrane can successfully restore deep corneal ulcers associated with persistent epithelial defects. When such defects are not associated with stromal ulcers, they might benefit from amniotic membrane grafts sutured to cover the entire corneal surface. Both methods may serve as valuable tools for ocular surface reconstruction, especially in the context of impaired epithelial function.

Amnion↗
PubMed1999

Topical application of methotrexate for inhibition of corneal angiogenesis.

PURPOSE: Methotrexate (MTX) is a folic acid antagonist used in chemotherapy regimens. Additional therapeutic applications have been suggested based on effect as an immuno-modulating drug in systemic rheumatoid disease and associated uveitis. Since chronic inflammatory disease is often associated with a neovascular response, we investigated the use of MTX for treatment of corneal angiogenesis. METHODS: Neovascularizations were induced by fibroblast growth factor in a corneal pocket model. Vessels were examined biomicroscopically. MTX was applied topically to rabbit corneas in a concentration of 0.2 mg/day. MTX level was measured in aqueous humor and plasma. RESULTS: On day 9 the vascularized area was 12.0+/-6.9 mm(2) in control eyes and significantly smaller, 2. 2+/-1.86 mm(2), in treated eyes. Treated animals showed no local side effects such as epithelial defects. Although therapeutic levels were measured in the aqueous humor, MTX could not be detected in the serum of treated animals. CONCLUSION: The antiangiogenic mechanism of MTX might be due to inhibition of both macrophage invasion during early angiogenesis and endothelial cell proliferation. The high levels in the aqueous humor indicate a possible application of topical MTX for inflammations of the anterior segment of the eye.

Animals↗
PubMed1999

Multilayer amniotic membrane transplantation for reconstruction of deep corneal ulcers.

PURPOSE: To evaluate the efficacy of multilayer amniotic membrane transplantation for reconstruction of corneal epithelium and stroma in the context of deep corneal ulcers. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Eleven consecutive patients with deep corneal ulcers refractory to conventional treatment; six patients had herpetic keratitis and five had other forms of neurotrophic keratitis. INTERVENTION: Multilayer amniotic membrane transplantation with kryopreserved human amniotic membrane. MAIN OUTCOME MEASURES: Integrity of corneal epithelium and stroma, opacification, and appearance of grafted membrane during 12 months follow-up. RESULTS: Amniotic membrane transplantation markedly reduced ocular inflammation in all patients. Epithelium healed above all corneal ulcers within 4 weeks and remained stable in 9 of 11 patients for 1 year. Two patients with recurrent epithelial defect suffered from severe neurotrophic keratitis. Following transplantation the amniotic membranes gradually dissolved over a period of 12 months, but stromal thickness remained stable. CONCLUSION: Amniotic membrane transplantation allows corneal surface reconstruction in patients with persistent epithelial defects. The multilayer technique is useful for treating deep corneal ulcers and even descemetoceles. Because the procedure results in stability of the ocular surface over a period of more than 12 months in most patients, it may be considered an alternative to conventional surgical techniques for ocular surface reconstruction.

Adult↗
PubMed1999

In vivo significance of ICAM-1--dependent leukocyte adhesion in early corneal angiogenesis.

PURPOSE: Numerous investigations have stressed the significance of leukocytes in early angiogenesis. Leukocytes invade the cornea, and the location of their extravasation corresponds to the site of vessel ingrowth. The interactions between leukocytes and vascular endothelium are mediated by various proteins, including adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). In this study, the role of ICAM-1 during early corneal angiogenesis was evaluated in vivo. METHODS: Corneal neovascularization was induced in New Zealand White rabbits by use of intrastromal pellets containing 750 ng vascular endothelial growth factor (VEGF). The fluorescent dye rhodamine 6G was used to stain leukocytes in vivo. Leukocyte adhesion and vessel growth were quantified in vivo by high-resolution fluorescence angiography. To inhibit ICAM-1 interactions a microemulsion containing anti-ICAM-1 antibody was applied topically. RESULTS: Limbal vessels showed increased leukocyte adhesion 24 hours after pellet implantation: The number of rolling and sticking leukocytes was significantly increased compared with the number in control animals (P < 0.01). Treatment with anti-ICAM-1 antibody resulted in reduced leukocyte sticking and increased leukocyte rolling. The area covered by new blood vessels was significantly diminished in eyes treated with anti-ICAM-1 (P < 0.05). CONCLUSIONS: The results support the hypothesis that ICAM-1-mediated leukocyte adhesion is a key event in early angiogenesis. This model may serve for investigation of the significance of adhesion molecules by in vivo observation and quantification.

Animals↗
PubMed1999

Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin.

PURPOSE: To investigate the effect of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2-E) on degradative functions of lysosomes in human retinal pigment epithelial (RPE) cells and to evaluate its mechanism of action. METHODS: A2-E was coupled to low-density lipoprotein (LDL). Human RPE cell cultures were loaded with the A2-E/LDL complex, and controls were run with medium containing LDL alone. To determine whether A2-E accumulated in lysosomes, cells were fractionated in a Percoll gradient, and protein degradation was determined by metabolic labeling and measurement of the release of low-molecular-weight radioactivity. Lysosomal degradation was distinguished from nonlysosomal degradation by inclusion of NH4Cl in the medium. The metabolism of sulfated glycosaminoglycans was studied by radiosulfate incorporation in pulse-chase experiments. Intralysosomal pH was determined using a fluorescent lysosomotropic pH indicator. RESULTS: A2-E accumulated almost exclusively in the lysosomal compartment. Lysosomal protein degradation was reduced in a dose-dependent fashion in A2-E-treated cells. The selectivity of A2-E on lysosomal function was demonstrated by its lack of effect on degradation of extralysosomal protein. Lysosomal glycosaminoglycan catabolism of RPE cells was also strongly inhibited by A2-E. Lysosomal pH was increased by A2-E. CONCLUSIONS: The findings indicate that accumulation of A2-E in RPE cells interferes with lysosomal functions as exemplified by its inhibitory effect on protein and glycosaminoglycan catabolic pathways. The quaternary amine character of the A2-E apparently causes a perturbation of the acidic intralysosomal milieu, resulting in diminished hydrolase action and consequent accumulation of undegraded material. Such mechanism could be operative in retinal diseases associated with excessive lipofuscin accumulation including age-related macular degeneration.

Adult↗
PubMed1999

Bone morphogenetic proteins and growth and differentiation factors in the human cornea.

PURPOSE: To investigate transcription of members of the transforming growth factor (TGF)-beta superfamily and corresponding receptors in human corneal epithelium and stroma. METHODS: Transcription of bone morphogenetic proteins (BMP)-2, BMP-3, BMP-4, BMP-5, and BMP-7; growth- differentiation factor (GDF)-5), and BMP receptors (BMPR) types I (BMPR-IA, BMPR-IB) and II (BMPR-II) was investigated by reverse transcription-polymerase chain reaction (RT-PCR) in ex vivo and cultured cells. For verification, PCR fragments were cloned and sequenced. DNA dot blot analysis was performed to estimate the level of transcription. RNA dot blots were performed to determine expression of GDF-5. Expression of BMP receptor proteins was investigated by immunohistochemistry. Single-cell clonal growth proliferation assays were performed using recombinant human GDF-5 and TGF-beta1. RESULTS: Transcription of BMP-2, BMP-3, BMP-4, BMP-5, and BMP-7 and receptors of BMPR-IA, BMPR-IB and BMPR-II was detected in ex vivo and cultured epithelium and stroma. The level of transcription was higher in cultured stroma for all factors, but the level for the receptors was higher in cultured epithelium. In contrast GDF-5 was transcribed only in stromal cells, suggesting that this cytokine may be an important mediator between keratocytes and epithelial cells. Furthermore, GDF-5 inhibited proliferation of corneal epithelial and stromal cells. CONCLUSIONS: Given the importance of the TGF-beta family during embryonic development, the results suggest that its members may be components of the corneal cytokine network and may participate in the regulation of cellular proliferation and differentiation.

Animals↗
PubMed1998

[Transplantation of amniotic membrane for reconstruction of the eye surface].

Persistent defects of the ocular surface remain a therapeutic challenge that often requires surgical intervention. Recently, the transplantation of human amniotic membrane has been added to our therapeutic armentarium. This thick basement membrane has distinct biological properties that influence cellular differentiation and proliferation. Amniotic membrane obtained from cesarean deliveries is prepared and cryopreserved under sterile conditions and can be sutured onto the ocular surface. This procedure allows for reepithelialization of persistent corneal ulcerations as well as filling of stromal defects. Amniotic membrane can successfully be employed for ocular surface reconstruction following large corneal excisions and in the context of limbal stem cell disease for pterygium surgery as well as for various kinds of reconstruction of the conjunctiva. Taken together, amniotic membrane transplantation can serve as a valuable tool for ocular surface reconstruction, especially in the context of impaired epithelial function.

Amnion↗