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Bernd Kirchhof

Publications and source records attributed to Bernd Kirchhof.

At least 19 recordsLinked to original sources
PubMed2006

Histological evidence for revascularisation of an autologous retinal pigment epithelium--choroid graft in the pig.

BACKGROUND: Translocation of a free autologous graft consisting of retinal pigment epithelium (RPE), Bruch's membrane, choriocapillaris and choroid in patients with exudative age-related macular degeneration is currently being evaluated in clinical practice. Angiographic studies in these patients suggest that their grafts become revascularised. AIM: To investigate the histological evidence of revascularisation of the graft in a porcine model. METHODS: In 11 pigs (11 eyes), an RPE-choroid graft was translocated from the mid-periphery to an intact or an intentionally damaged RPE and Bruch's membrane at the recipient site. The eyes were enucleated 1 week or 3 months after surgery. Tissue sections were evaluated using immunohistochemistry. RESULTS: Bridging vessels between recipient layer and graft were identified from 1 week to 3 months after surgery. This reconnection occurred regardless of whether the Bruch's membrane of the recipient site was left intact or intentionally damaged at the time of transplantation. The vasculature of the graft appeared open and perfused. Vessels with transcapillary pillars and conglomerates of small new vessels were present in the graft. CONCLUSIONS: This study showed histological evidence for revascularisation by angiogenesis of a free autologous RPE-choroid graft.

Animals↗
PubMed2006

Overexpression of FasL in retinal pigment epithelial cells reduces choroidal neovascularization.

Choroidal neovascularization (CNV) is responsible for the severe visual loss in age-related macular degeneration. CNV formation is considered to be due to an imbalance between pro- and antiangiogenic factors that lead to neovascular growth from the choriocapillaris into the subretinal space. To define whether FasL overexpression in retinal pigment epithelial cells (RPE) can inhibit choroidal neovascularization through Fas-FasL-mediated apoptosis, we examined the role of this pathway in a mouse model of laser-induced choroidal neovascularization. FasL was expressed in the retinal pigment epithelium of transgenic mice. Polymerase chain reaction (PCR), immunoblot, and immunohistochemistry confirmed that the transgene FasL was specifically expressed in RPE. The established laser model was used to induce choroidal neovascularization (CNV) in wild-type (WT) and transgenic mice. CNV formation was compared with respect to fluorescein angiographic leakage (at days 0 and 14 after laser injury) and histological appearance. The lesions were assessed on RPE-choroidal flatmounts after CD31-labeling and with confocal microscopy after perfusion with rhodamine-labeled concanavalin A (Con A). Apoptosis was quantified by TUNEL positivity and caspase activation. FasL mRNA and protein were highly expressed in the RPE of the transgenic mice before and after laser photocoagulation. In contrast, FasL was only weakly expressed in the RPE layer of WT C57BL/6J mice. While ruptures of Bruch's membrane and CNV formation were observed histologically two weeks after laser photocoagulation in transgenic as well as control eyes, the shape and size of CNV lesions were reduced in the transgenic mice. The area of leakage was decreased by 70% in FasL transgenic mice compared with WT mice (P<0.005). The number of TUNEL-positive cells was greater in FasL-overexpressing mice and correlated with the expression of activated caspases. Th expression of other antiangiogenic factors such as PEDF remained unchanged. The specific overexpression of FasL in RPE layer reduced CNV formation in our laser model. Our results strongly point to the FasL-Fas pathway as a potential therapeutic target in controlling pathological choroidal neovascularization.

Animals↗
PubMed2006

Autologous translocation of the choroid and retinal pigment epithelium in age-related macular degeneration.

PURPOSE: To evaluate the autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in 45 eyes of 43 patients with age-related macular degeneration (AMD). DESIGN: Prospective nonrandomized study. METHODS: All patients had visual loss due to AMD (n = 5 classic membranes, n = 14 occult, n = 2 mixed, n = 16 pigment epithelial detachment (PED), n = 5 subretinal hemorrhage, n = 3 geographic atrophy). After extraction of the neovascular complex, an autologous peripheral full-thickness explant of RPE, Bruch membrane, and choroid was translocated from the midperiphery to the macula. RESULTS: Preoperative distant visual acuity ranged from 20/800 to 20/40. Reading vision ranged from 1.4 logarithm of reading acuity determination (logRAD) to 0.5 logRAD (0.04 to 0.32 Snellen equivalent). Revision surgery was required in 22 eyes as a result of proliferative vitreoretinopathy (PVR), retinal detachment, macular pucker, or vitreous hemorrhage. In eight patients, the patch was renewed. At six months, distant visual acuity ranged from light perception to 20/50 (increase of 15 letters in four eyes). Reading vision ranged from 1.4 to 0.4 logRAD. Visual outcome was unrelated to the type of AMD. Vascularization of the transplant was visible on indocyanine green (ICG) angiography in 40 of 42 eyes. In most patients, autofluorescence of the pigment epithelium was coincident with revascularization of the graft. Fixation on the patch was positively related to visual acuity. CONCLUSIONS: Autologous translocation of a full-thickness transplant of choroid and RPE usually results in a vascularized and functioning graft. Vascularization was even achieved in patients with geographic atrophy. Fixation stability and microperimetry before the patch translocation may be helpful in selecting patients who will profit from surgery.

Aged↗
PubMed2006

Characteristics of iris and retinal pigment epithelial cells cultured on collagen type I membranes.

PURPOSE: Transplantation of pigment epithelial cells is a promising treatment modality to repair retinal damage in age-related macular degeneration. For this purpose, it is necessary to establish cell culture techniques that allow acquisition of proper functional and morphological characteristics by the cells to be transplanted. METHODS: Primary retinal pigment epithelial (RPE) and iris pigment epithelial (IPE) cells grown to confluence on collagen membranes were examined for morphology, adhesion, proliferation, apoptosis, as well as viability after ex vivo transplantation. RESULTS: Pigment epithelial cells adhere, proliferate, form monolayers, acquire differentiated properties, and remain viable during transplantation to the subretinal space. CONCLUSIONS: Pigment epithelial cells cultured on collagen membranes acquire differentiated characteristics and are amenable to be transplanted as cell monolayers.

Animals↗
PubMed2005

Effects of daunorubicin and CD95L on retinal function in superfused vertebrate retina.

Alternative treatments of proliferative vitreoretinopathy (PVR) are needed. The intravitreal application of daunorubicin combined with CD95 ligand (CD95L) could provide a new therapeutic strategy. The effects of this application on bovine retinal function were investigated. Bovine retina preparations were perfused with a standard solution preequilibrated with oxygen. The b-wave and, after the addition of aspartate, the photoreceptor potential P III of the electroretinogram (ERG) were recorded using Ag/AgCl electrodes. Stable ERG amplitudes were recorded, then daunorubicin was added to the solution for 45 minutes, also with the addition of CD95L antibody. Subsequently, the preparation was reperfused with the standard solution for 100 minutes, to allow for recovery. The reduction in b-wave amplitude was reversible and not significantly changed by the addition of 0.25 microg/mL CD95L antibody to 13 microM of daunorubicin. The reduction of the b-wave amplitude was significantly changed and only partly reversible within the recovery time using 40 microM and 80 microM of daunorubicin. The photoreceptor potential P III amplitude was not significantly changed for up to 80 microM of daunorubicin. The ERG showed toxic effects of daunorubicin above a concentration of 13 microM used therapeutically in humans. The combination with CD95L did not increase retinal toxicity. It is, therefore, concluded that daunorubicin may be applied intraocularly, combined with CD95L, without interfering with retinal function.

Animals↗
PubMed2004

Influence on membrane-mediated cell activation by vesicles of silicone oil or perfluorohexyloctane.

PURPOSE: This study was conducted to investigate whether macrophage activation through cell membrane attachment might be supported by emulsified tamponade droplets of a certain vesicle size. It has been hypothesized that emulsification of vitreous tamponades might stimulate retinal membrane formation. METHODS: In this laboratory investigation, similarly sized vesicles of silicone oil and the partially fluorinated alkane perfluorohexyloctane (F6H8) were produced by extrusion through polycarbonate membranes. Human neutrophils were obtained from blood donors. Human monocytes were negatively isolated from mononuclear cells by depletion of other cells. Cell activation status of phagocyting blood neutrophils was measured by a chemiluminescence assay. Fluorescent attached or internalized vesicles were monitored by fluorescent microscopy. The main outcome measures were the altered activation status of monocytes after vesicle incubation and the ability of human macrophages to attach and/or internalize vesicles in vitro. RESULTS: Extruding silicone oil through a polycarbonate membrane resulted in the production of vesicles that remained stable for at least 2 days. F6H8 vesicles had to be stabilized with an emulsifier, in this case Pluronic PE6800 or Lipoid EPC. The mean vesicle diameter was similar with both components (F6H8: 13.08+/-2.95 microm, silicone oil: 10.05+/-4.6 microm). Neutrophil activation was not influenced by either emulsifier alone or by silicone oil vesicles without emulsifier. Stabilized F6H8 vesicles had a dose-dependent influence on blood neutrophil activation. Only silicone oil vesicles together with Lipoid EPC, not Pluronic PE6800, had a comparable influence on neutrophil activation. Neutrophil activation was influenced neither by 0.125% human serum albumin (HSA) alone nor by vesicles of F6H8 or silicone oil prepared with 0.125% HSA. Monocyte cell membrane attachment of silicone fluid was two times higher than that of F6H8 fluid. F6H8/Pluronic PE6800 vesicles enhanced this process 20-fold, whereas silicone oil vesicles did not enhance cell membrane attachment significantly. CONCLUSIONS: These in vitro data do not support the hypothesis that emulsification of the tamponades silicone oil or F6H8 in the microenvironment of the eye might easily activate neutrophils or stimulate phagocytosis by monocytes. A prerequisite is the combination of a vesicle shape of the tamponades with specific stabilizing or modifying surfactants. Emulsified tamponades stabilized by artificial surfactants, but not by the naturally occurring protein HSA, favor cell activation by cell membrane attachment.

Cytoplasmic Vesicles↗
PubMed2004

Strategies to influence PVR development.

Proliferative vitreo-retinopathy (PVR) is a complication of rhegmatogenous retinal detachment or severe ocular trauma (intraocular foreign body, penetration, perforation, contusion, rupture). The risk of PVR varies from 10 to 40% depending on the original disease. Strategies to influence the risk of PVR include surgical techniques, pharmacological adjuncts, and preventive measurements. Surgical influences on the risk of PVR comprise: surgical skills (buckling, atraumatic procedure), primary vitrectomy, early vitrectomy, retinectomy, choice of vitreous tamponade agent. The influence of most such parameters is not confirmed by prospective randomized studies. Pharmaceutical adjuncts include daunomycin, 5-fluoruracil plus heparin and others. The influence of most such parameters has been studied by prospective randomized studies. The effect is statistically significant, its clinical relevance is subject of current discussion. Prevention of PVR, via prevention of injury, was successful in the past as shown by the reduction of wind screen injuries after the seatbelt legislation was installed, and reduction of work related injuries from protective eyewear. As for the treatment of existent PVR despite some progress in the past, there should be better ways of treatment ahead of us.

Chemotherapy, Adjuvant↗
PubMed2004

Translocation of iris pigment epithelium in patients with exudative age-related macular degeneration: long-term results.

PURPOSE: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (ARMD) over 1 year. METHODS: The consecutive interventional case series included 56 patients with exudative ARMD. During vitrectomy the submacular neovascular membrane (CNV) was removed and IPE cells, harvested from a peripheral iridectomy, were injected into the submacular space. Included were patients with subfoveal occult CNV (11 eyes), classic CNV (10 eyes), mixed CNV (17 eyes), CNV with a pigment epithelial detachment (13 eyes) or CNV with a hemorrhage (5 eyes). Outcome measures were visual acuity, foveal fixation, size of CNV and rate of recurrence based on fluorescence angiographic imaging. RESULTS: All patients underwent successful surgical removal of the CNV with consecutive subretinal IPE injection. Visual acuity was better than 20/100 in 19 patients preoperatively and in 18 patients postoperatively. A visual acuity of 20/100 or less was found in 37 patients preoperatively and in 38 patients postoperatively. Mean preoperative visual acuity (1.0+/-0.3 logMAR units) did not change significantly after 1 year (1.0+/-0.3 logMAR units). Ten eyes (18%) developed a recurrence. Fixation within the surgically denuded area could be demonstrated in 25 eyes (45%). CONCLUSIONS: Autologous IPE translocation for ARMD over one year can preserve foveal function on a low level, but cannot improve visual acuity. IPE translocation is technically feasible with a low rate of complications. Continued research seems justified to improve functional outcome.

Aged↗
PubMed2004

A central role for inflammation in the pathogenesis of diabetic retinopathy.

Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and nonperfusion. Diabetic retinal vascular leakage, capillary nonperfusion, and endothelial cell damage are temporary and spatially associated with retinal leukocyte stasis in early experimental diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1) and CD18. Mice deficient in the genes encoding for the leukocyte adhesion molecules CD18 and ICAM-1 were studied in two models of diabetic retinopathy with respect to the long-term development of retinal vascular lesions. CD18-/- and ICAM-1-/- mice demonstrate significantly fewer adherent leukocytes in the retinal vasculature at 11 and 15 months after induction of diabetes with STZ. This condition is associated with fewer damaged endothelial cells and lesser vascular leakage. Galactosemia of up to 24 months causes pericyte and endothelial cell loss and formation of acellular capillaries. These changes are significantly reduced in CD18- and ICAM-1-deficient mice. Basement membrane thickening of the retinal vessels is increased in long-term galactosemic animals independent of the genetic strain. Here we show that chronic, low-grade subclinical inflammation is responsible for many of the signature vascular lesions of diabetic retinopathy. These data highlight the central and causal role of adherent leukocytes in the pathogenesis of diabetic retinopathy. They also underscore the potential utility of anti-inflammatory treatment in diabetic retinopathy.

Animals↗
PubMed2004

Visual outcome of patients with macular edema after pars plana vitrectomy and indocyanine green-assisted peeling of the internal limiting membrane.

PURPOSE: To evaluate the efficacy of inner limiting membrane (ILM) peeling in persistent macular edema. METHODS: This retrospective review analyzed a series of 23 eyes from 23 patients with persistent macular edema treated by pars plana vitrectomy (PPV) with indocyanine green (ICG)-assisted peeling of the ILM. Thirteen female and 10 male patients with a mean age of 57.2+/-15.6 (24-77) years underwent operation between May 2000 and October 2001. The main diagnoses were uveitis (anterior, intermediate, posterior and panuveitis) ( n=9), central retinal vein occlusion (CRVO) (n=4), diabetic retinopathy (DR) ( n=5), vitreoretinal traction syndrome ( n=2), and Irvine-Gass syndrome ( n=3). Nine eyes had undergone phacoemulsification (PE) previously and two eyes had been subjected to combined PE and ILM peeling. The eyes were tamponaded with gas (3), silicone oil (5) or air (11). In four cases no endotamponade was used. Improvement in visual acuity of 2 lines or more was regarded as significant. RESULTS: Visual acuity improved after 3 months in 9 of the 23 patients. After 6 months and at the follow-up, a significant improvement was found in 6/21 and 7/21 patients. This improvement was predominantly seen in patients with uveitis (5/9), or diabetic maculopathy (3/5); One patient with Irvine-Gass syndrome showed a significant reduction, one with vitreoretinal traction an improvement in visual acuity. The group of patients with CRVO showed no significant change during the follow-up. The choice of endotamponade did not alter the visual acuity outcome. CONCLUSIONS: Different patient groups respond differently to ILM peeling. Although overall significant visual acuity improvement was observed in only one third of all cases 12 months after ILM peeling for persistent macular edema, patients with uveitis and nonproliferative diabetic maculopathy demonstrated a benefit. The lack of long-term improvement in the majority of cases is in accordance with the hypothesis that ILM peeling may reduce the intraretinal edema, but does not affect the underlying mechanism causing macular edema. So far, only diabetics have shown improvement (still unproven) from ILM peeling, and this study provides no justification for extending the treatment to macular edema of other causes. Large-scale investigations are needed to evaluate the efficacy in certain diagnosis groups.

Adult↗
PubMed2004

Activin a in the regulation of corneal neovascularization and vascular endothelial growth factor expression.

Activin A, a dimeric glycoprotein that belongs to the transforming growth factor-beta superfamily, governs cellular differentiation in a wide variety of models and has been implicated in the regulation of angiogenesis. We examined the role of activin A and its downstream signaling pathway in a murine model of inflammatory corneal neovascularization induced by mechanical injury (debridement), and in vitro in corneal epithelial cells. Activin A expression increased steadily from day 2 until day 8 after mechanical debridement in vivo, paralleling vascular endothelial growth factor (VEGF) expression. Administration of recombinant activin A in mice increased the area of neovascularization, VEGF expression, and the kinase activities of p38 and p42/44 MAPKs after mechanical debridement. Systemic inhibition of activin A in vivo with a neutralizing antibody reduced the area of neovascularization, VEGF expression, and p38 and p42/44 MAPK activity, whereas administration of an isotype-matched control antibody had no effect. In vitro treatment with activin A increased VEGF secretion, as well as p38 and p42/44 MAPK activity in corneal epithelial cells, whereas concurrent administration of specific inhibitors of p38 or p42/44 MAPK abolished the stimulatory effect of activin A on VEGF production. We conclude that activin A stimulates inflammatory corneal angiogenesis by increasing VEGF levels through a p38 and p42/44 MAPK-dependent mechanism.

Activins↗
PubMed2003

Electro-oculographic findings after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in age-related macular degeneration.

PURPOSE: To evaluate potential electro-oculographic changes after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age-related macular degeneration (AMD) in a randomised comparative (self-controlled) trial. METHODS: A consecutive series of 30 patients suffering from subfoveal choroidal neovascularisation secondary to age-related macular degeneration underwent 360 degrees retinotomy and macular translocation. The EOG served as the main parameter of the study and was recorded 1 day prior to the translocation surgery and no earlier than 21 days after the silicone oil removal. RESULTS: Postoperatively, a statistically significant decrease in mean dark trough by 64% was found for treated eyes (P<0.001). The mean dark trough of the fellow eye remained stable after surgery (P=0.33). The postoperative difference between the treated und untreated eyes proved to be statistically significant (P<0.001). The Arden ratio remained stable in the treated and untreated eyes with mean values of 204% (P=0.81) and 213% (P=0.18), respectively. A significant correlation between the reduction of the dark trough and the visual acuity at the 1-year follow-up was found. CONCLUSIONS: A persistent decrease in the corneofundal potential is associated with 360 degrees retinotomy and macular translocation for exudative AMD. This indicates a substantial postoperative malfunction of retinal pigment epithelial cells and an impaired photoreceptor regeneration. The impeded recovery of the RPE-photoreceptor complex can be interpreted as the result of the surgical trauma on the basis of prediseased RPE. A severe postoperative decrease in dark trough forecasts an incomplete recovery of visual acuity.

Choroidal Neovascularization↗
PubMed2003

Neodymium:YAG laser capsulotomy in vitrectomized pseudophakic eyes with persistent endotamponade.

PURPOSE: To evaluate the feasibility and limits of neodymium:YAG (Nd:YAG) laser capsulotomy in eyes with persistent endotamponade. SETTING: Department of Ophthalmology, University Cologne, Cologne, Germany. METHODS: In this consecutive series, an Nd:YAG laser capsulotomy was performed by 1 surgeon in 6 eyes with posterior capsule opacification (PCO) and persistent endotamponade caused by proliferative vitreoretinopathy. The endotamponade was with silicone oil (5000 centistokes) in 5 eyes and with perfluorohexyloctane (F(6)H(8)) in 1 eye. Also evaluated were 6 vitrectomized eyes without endotamponade that had an Nd:YAG laser capsulotomy for PCO by the same surgeon. All 12 eyes were pseudophakic. The mean follow-up after capsulotomy was approximately 6 months (range 2 to 12 months). Follow-up examinations included visual acuity, intraocular pressure measurement, and IOL centration and capsule reopacification evaluation. RESULTS: The total energy required was higher in eyes with persistent endotamponade. In 3 of these eyes, the laser capsulotomy could not be successfully completed and was surgically enhanced. The laser capsulotomy in eyes without endotamponade was successful in all cases. Complete reopacification occurred in 2 eyes with persistent endotamponade within 2 months and in no eye without endotamponade. Improvement in visual acuity was limited in all eyes because of retinal pathology. CONCLUSIONS: Neodymium:YAG laser capsulotomy in pseudophakic eyes with persistent endotamponade was successful but had a relatively high reintervention rate. The visual prognosis was limited in all cases because of retinal pathology.

Adult↗
PubMed2003

The effect of membrane differential filtration on the colloid osmotic pressure in patients with age-related macular degeneration: significance to visual function?

To investigate the effect of membrane differential filtration (MDF) on plasma colloid osmotic pressure (COP) and visual functions in age-related geographic macular degeneration (AMD). Ten consecutive patients with non-exudative AMD underwent one MDF cycle. Primary endpoint was COP. Secondary endpoints were visual acuity and the mean defect of visual field. The COP was markedly reduced after one MDF cycle by 23.9% (P = 0.001). Compared with the baseline examination, visual acuity and the mean defect of visual field improved significantly after MDF. A significant positive correlation was found between the improvement in visual field and the decrease in COP (Pearson's coefficient = 0.65; P = 0.04). Membrane differential filtration lowers plasma colloid osmotic pressure in patients with non-exudative AMD. Based on the observation that visual field and COP are correlated, one may hope for a means to improve decreased central retinal function in eyes with geographic AMD by modulation of COP plasma level.

Female↗