Reproducibility and Daytime-Dependent Changes of Corneal Epithelial Thickness and Whole Corneal Thickness Measured With Fourier Domain Optical Coherence Tomography.

To evaluate the reproducibility of Fourier domain anterior segment optical coherence tomography (RTVue) based on repeated measurements of corneal thickness (CT) and epithelial thickness (ET) and to test daytime-dependent changes of these parameters.Twenty-three eyes from 23 healthy volunteers were included in this prospective study. Three clinical observers performed 3 consecutive measurements each of CT and ET in 3 sessions using RTVue, resulting in 9 measurements per session. Session 1 was performed at 9 AM ± 1 hour, session 2 at 4 PM ± 1 hour on the same day, and session 3 at 9 AM ± 1 hour 2 days later. CT and ET were assessed in 9 areas: corneal vertex, 4 paracentral zones, and 4 periph…

Polyphosphate, the physiological metabolic fuel for corneal cells: a potential biomaterial for ocular surface repair

The regeneration of the epithelium, covering the avascular cornea, involves the processes of differentiation, proliferation and migration of cells originating from the corneal epithelial stem cells. We ask the question if these energy-consuming processes can be fueled by the physiological, inorganic polyphosphate (polyP), the main energy storage/donor molecule in the extracellular space. The ex vivo results reveal that addition of polyP, in the form of soluble Na-polyP, to the culture medium elicits a strong stimulatory effect on cell viability/growth and migration of corneal epithelial cells. Microscopic analyses of partially denuded cornea specimens show that in the presence of polyP, but…

Topical Voriconazole as Supplemental Treatment for Acanthamoeba Keratitis

Purpose Voriconazole was shown to inhibit ergosterol synthesis in various acanthamoeba species. The purpose of this study was to evaluate the clinical outcome of treatment with supplemental topical voriconazole in patients with acanthamoeba keratitis (AK). Methods All patients who had been treated for AK with voriconazole 1% drops in conjunction with topical first-line antiacanthamoeba therapy composed of polyhexamethylene biguanide (PHMB) 0.02% and propamidine isethionate 0.1% (Brolene) between November 2014 and August 2017 at the Department of Ophthalmology, University Medical Center Mainz, were included. The main outcomes were treatment failure and recurrence rate. Secondary outcomes wer…

Effects of Superficial Keratectomy in Peripheral Hypertrophic Subepithelial Corneal Opacification on Front and Back Corneal Astigmatism

To evaluate changes of anterior and posterior corneal astigmatism after superficial keratectomy in peripheral hypertrophic subepithelial corneal opacification (PHSCO). Patients with PHSCO, who had ...

Comparison of DMEK and DSAEK in Eyes With Endothelial Decompensation After Previous Penetrating Keratoplasty.

PURPOSE Posterior lamellar keratoplasty is increasingly applied in patients with endothelial decompensation after penetrating keratoplasty (PK). The aim of this study was to compare the results of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) after PK. METHODS In this retrospective study, clinical data of 30 patients who received DMEK (n = 19) or DSAEK (n = 11) for endothelial decompensation after PK were evaluated. All lamellar keratoplasties were performed at the Department of Ophthalmology at University Hospital Mainz, Germany. Primary end point included best-corrected visual acuity, and secondary end points included e…

Expansion und Transplantation limbaler Stammzellen zur Regeneration der kornealen Oberfläche

ZusammenfassungDie Regeneration des Hornhautepithels wird beim Menschen über das Stammzellreservoir des Limbus reguliert. Bei ausgedehnter Zerstörung der Limbusregion im Rahmen von Entzündungen, Verbrennungen oder Verätzungen kann sich eine limbale Stammzellinsuffizienz ausbilden, bei der es zu einer Vaskularisation und Eintrübung der Hornhaut mit funktioneller Beeinträchtigung kommen kann. Es stehen verschiedene Verfahren der autologen und allogenen Transplantation limbaler Stammzellen zur Verfügung. So können ganze Limbusabschnitte und kleine Limbusbiopsate direkt transplantiert oder aus kleinen Limbusbiopsaten stammende Zellen zunächst ex vivo auf Trägermembranen vermehrt und anschließen…

Postoperative Repositioning of Inverted Descemet Membrane Endothelial Keratoplasty Grafts

Item does not contain fulltext PURPOSE: To present 4 cases of postoperative repositioning of inverted grafts after Descemet membrane endothelial keratoplasty (DMEK). METHODS: Retrospective case reports of 4 patients presenting with subtotal to total graft detachment after DMEK, most probably owing to upside-down graft positioning. Graft repositioning was performed 1 to 14 days after initial DMEK surgery. In 3 cases (cases 1, 3, and 4), repositioning was performed without removing the graft from the anterior chamber (AC), whereas for case 2, the graft had to be removed from the AC to attain correct graft orientation. RESULTS: In all 4 cases, the initially upside-down DMEK grafts could be suc…

Preparation Steps for Measurement of Reactivity in Mouse Retinal Arterioles <em>Ex Vivo</em>

Vascular insufficiency and alterations in normal retinal perfusion are among the major factors for the pathogenesis of various sight-threatening ocular diseases, such as diabetic retinopathy, hypertensive retinopathy, and possibly glaucoma. Therefore, retinal microvascular preparations are pivotal tools for physiological and pharmacological studies to delineate the underlying pathophysiological mechanisms and to design therapies for the diseases. Despite the wide use of mouse models in ophthalmic research, studies on retinal vascular reactivity are scarce in this species. A major reason for this discrepancy is the challenging isolation procedures owing to the small size of these retinal blo…

Cardiovascular and ocular safety of α1-adrenoceptor antagonists in the treatment of male lower urinary tract symptoms

α1-Adrenoceptor antagonists (α-blockers) represent first-line drug treatment for male lower urinary tract symptoms. Their adverse events (AEs) include asthenia, dizziness, nasal congestion, arterial (orthostatic) hypotension and intraoperative floppy iris syndrome (IFIS).This report focuses on cardiovascular and ocular AEs of α-blockers as related to their mechanism of action and subtype selectivity.The incidence of hypotension differs between α-blockers. It is greatest with doxazosin or terazosin, but others including tamsulosin can also lead to hypotension especially upon treatment initiation. Concomitant antihypertensive medication increases the incidence of hypotension with some α-block…

Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cel…

Chronic social defeat stress causes retinal vascular dysfunction

Abstract Purpose The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss. Methods Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively.…

Identification of the Muscarinic Acetylcholine Receptor Subtype Mediating Cholinergic Vasodilation in Murine Retinal Arterioles

To identify the muscarinic acetylcholine receptor subtype that mediates cholinergic vasodilation in murine retinal arterioles.Muscarinic receptor gene expression was determined in murine retinal arterioles using real-time PCR. To assess the functional relevance of muscarinic receptors for mediating vascular responses, retinal vascular preparations from muscarinic receptor-deficient mice were studied in vitro. Changes in luminal arteriole diameter in response to muscarinic and nonmuscarinic vasoactive substances were measured by video microscopy.Only mRNA for the M(3) receptor was detected in retinal arterioles. Thus, M(3) receptor-deficient mice (M3R(-/-)) and respective wild-type controls …

Short-Time Ocular Ischemia Induces Vascular Endothelial Dysfunction and Ganglion Cell Loss in the Pig Retina

Visual impairment and blindness are often caused by retinal ischemia-reperfusion (I/R) injury. We aimed to characterize a new model of I/R in pigs, in which the intraocular pathways were not manipulated by invasive methods on the ocular system. After 12 min of ischemia followed by 20 h of reperfusion, reactivity of retinal arterioles was measured in vitro by video microscopy. Dihydroethidium (DHE) staining, qPCR, immunohistochemistry, quantification of neurons in the retinal ganglion cell layer, and histological examination was performed. Retinal arterioles of I/R-treated pigs displayed marked attenuation in response to the endothelium-dependent vasodilator, bradykinin, compared to sham-tre…

Intraocular pressure measurements during flap preparation using 2 femtosecond lasers and 1 microkeratome in human donor eyes

Purpose To evaluate and compare intraocular pressures (IOPs) during flap preparations performed using 2 femtosecond lasers and a mechanical microkeratome in human donor globes. Setting University Medical Center Mainz, Mainz, and Euroeyes Clinic Stuttgart, Stuttgart, Germany. Design Experimental study. Methods A cannula was inserted through the optic nerve in human globes. The IOP was obtained continuously during flap preparation using the 60 kHz Intralase femtosecond laser, the 200 kHz Visumax femtosecond laser, or the Amadeus II microkeratome. For each experiment, a normal lamellar flap preparation (regular procedure) and a worst-case procedure (femtosecond laser interface was pressed agai…

Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina

Ischemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 110 mm Hg for 45 min, while the fellow eye served as a control. One group of mice received betulinic acid (50 mg/kg/day p.o. once daily) and the other group received the vehicle solution only. Eight days after the I/R event, the animals were killed and the retinal wholemounts and optic nerve cross-sections were prepared and stained with cresyl blue or toluidine blue, respectively, to count cells in…

Aircraft noise exposure drives the activation of white blood cells and induces microvascular dysfunction in mice

Epidemiological studies showed that traffic noise has a dose-dependent association with increased cardiovascular morbidity and mortality. Whether microvascular dysfunction contributes significantly to the cardiovascular health effects by noise exposure remains to be established. The connection of inflammation and immune cell interaction with microvascular damage and functional impairment is also not well characterized. Male C57BL/6J mice or gp91phox−/y mice with genetic deletion of the phagocytic NADPH oxidase catalytic subunit (gp91phox or NOX-2) were used at the age of 8 weeks, randomly instrumented with dorsal skinfold chambers and exposed or not exposed to aircraft noise for 4 days. Pro…

Role of α1-adrenoceptor subtypes on corneal epithelial thickness and cell proliferation in mice

Adrenergic stimuli are important for corneal epithelial structure and healing. The purpose of the present study was to examine the hypothesis that the lack of a single α1-adrenoceptor (α1-AR) subtype affects corneal epithelial thickness and cell proliferation. Expression levels of α1-AR mRNA were determined in mouse cornea using real-time PCR. In mice devoid of one of the three α1-AR subtypes (α1A-AR−/−, α1B-AR−/−, α1D-AR−/−) and in wild-type controls, thickness of individual corneal layers, the number of epithelial cell layers, and average epithelial cell size were determined in cryosections. Endothelial cell density and morphology were calculated in corneal explants, and epithelial cell p…

Elevated intraocular pressure induces neuron-specific β-III-tubulin expression in non-neuronal vascular cells.

Purpose Pathological alterations within optic nerve axons and progressive loss of the parental retinal ganglion cell (RGC) bodies are characteristics of glaucomatous neuropathy. Abnormally elevated intraocular pressure (IOP) is thought to be the major risk factor for most forms of glaucomatous changes, while lowering of the IOP is the mainstream of treatment. However, the pathophysiological mechanisms involved in neurodegenerative changes are poorly understood. It remains still a matter of debate whether elevated IOP harms the neurons directly or indirectly through alterations in the retinal vascularization. Methods We analysed morphological and molecular changes within the retina exposed t…

Role of the M3 Muscarinic Acetylcholine Receptor Subtype in Murine Ophthalmic Arteries After Endothelial Removal

We tested the hypothesis that the M3 muscarinic acetylcholine receptor subtype mediates cholinergic responses in murine ophthalmic arteries after endothelial removal.Muscarinic receptor gene expression was determined in ophthalmic arteries with intact and with removed endothelium using real-time PCR. To examine the role of the M3 receptor in mediating vascular responses, ophthalmic arteries from M3 receptor-deficient mice (M3R(-/-)) and respective wild-type controls were studied in vitro. Functional studies were performed in nonpreconstricted arteries with either intact or removed endothelium using video microscopy.In endothelium-intact ophthalmic arteries, mRNA for all five muscarinic rece…

The Role of Adrenoceptors in the Retina

The retina is a part of the central nervous system, a thin multilayer with neuronal lamination, responsible for detecting, preprocessing, and sending visual information to the brain. Many retinal diseases are characterized by hemodynamic perturbations and neurodegeneration leading to vision loss and reduced quality of life. Since catecholamines and respective bindings sites have been characterized in the retina, we systematically reviewed the literature with regard to retinal expression, distribution and function of alpha1 (α1)-, alpha2 (α2)-, and beta (β)-adrenoceptors (ARs). Moreover, we discuss the role of the individual adrenoceptors as targets for the treatment of retinal diseases.

Functional Role of α1-Adrenoceptor Subtypes in Murine Ophthalmic Arteries

PURPOSE To identify the α(1)-adrenoceptor (α(1)-AR) subtypes mediating vascular adrenergic responses in murine ophthalmic arteries. METHODS Expression of mRNA was quantified for individual α(1)-AR subtypes in murine ophthalmic arteries using real-time PCR. To assess the functional relevance of α(1)-ARs for mediating vascular responses, ophthalmic arteries from mice deficient in one of the three α(1)-AR subtypes (α(1A)-AR(-/-), α(1B)-AR(-/-), and α(1D)-AR(-/-), respectively) and wild-type controls were isolated, cannulated with micropipettes, and pressurized. Changes in luminal artery diameter in response to the α(1)-AR agonist phenylephrine, the sympathetic transmitter noradrenaline, and to…

In vivo analysis of noise dependent activation of white blood cells and microvascular dysfunction in mice

This article contains supporting information on data collection for the research article entitled “Aircraft noise exposure drives the activation of white blood cells and induces microvascular dysfunction in mice” by Eckrich et al. We found that noise-induced stress triggered microvascular dysfunction via involvement of innate immune-derived reactive oxygen species. In this article, we present the instrumentation of mice with dorsal skinfold chambers for in vivo microscopic imaging of blood flow, interaction of leukocytes with the vascular wall (also by fluorescent labelling of blood cells) and vessel diameter. In addition, we explain the preparation of cerebral arterioles for measurement of…

Neuroendocrine Modulation of IL-27 in Macrophages

Abstract Heterodimeric IL-27 (p28/EBV-induced gene 3) is an important member of the IL-6/IL-12 cytokine family. IL-27 is predominantly synthesized by mononuclear phagocytes and exerts immunoregulatory functional activities on lymphocytic and nonlymphocytic cells during infection, autoimmunity or neoplasms. There is a great body of evidence on the bidirectional interplay between the autonomic nervous system and immune responses during inflammatory disorders, but so far IL-27 has not been defined as a part of these multifaceted neuroendocrine networks. In this study, we describe the role of catecholamines (as mediators of the sympathetic nervous system) related to IL-27 production in primary …

Spontaneous Resolution of Delayed Suprachoroidal Hemorrhage in the Single Eye Following Needling in Congenital Glaucoma

Suprachoroidal hemorrhage (SCH) is a rare, but potentially vision-threatening event with poor long-term visual prognosis. At present, there is disagreement whether surgical intervention or conservative treatment is superior in the management. We report on a case of spontaneous resolution of severe SCH after needling procedure in the only eye of a young patient with congenital glaucoma.A 43-year-old woman with congenital glaucoma was scheduled for bleb needling in her only eye. Preoperative best-corrected visual acuity was 20/40 and intraocular pressure 20 mm Hg. On the third postoperative day, she developed a massive delayed SCH with appositional (kissing) choroidal bullae and visual acuity…

Entwicklung der Hornhautdicke während der UV-Vernetzungstherapie unter Anwendung verschiedener Kompositionen von Riboflavin-Augentropfen

Background During the UVA-cross-linking treatment in keratoconus patients, the UVA rays are partially absorbed in the stroma of the riboflavin-loaded cornea. This effect protects the corneal endothelium from UVA irradiation damage. The intensity of UVA light reaching the endothelium is inversely correlated with corneal thickness. The common composition of riboflavin eye drops may lead to a marked reduction in corneal thickness increasing the risk of endothelial damage. Patients and methods In a retrospective analysis of 23 UVA-cross-linking procedures on 23 patients we collected data about the pre-, intra- and postoperative corneal thickness (measured with ultrasound). Among these patients …

Utilization of metabolic energy in treatment of ocular surface disorders: polyphosphate as an energy source for corneal epithelial cell proliferation.

Impaired regeneration of the corneal epithelium, as found in many ocular surface diseases, is a major clinical problem in ophthalmology. We hypothesized that corneal epithelial regeneration can be promoted by the physiological, energy-delivering as well as “morphogenetically active” polymer, inorganic polyphosphate (polyP). Corneal limbal explants (diameter, 4 mm) were cultivated on collagen-coated well plates in the absence or presence of polyP (chain length, ∼40 Pi units; 50 μg ml−1) or human platelet lysate (hp-lysate; 5% v/v). Cell outgrowth and differentiation were analyzed after staining with DRAQ5 (nuclei) and rhodamine phalloidin (cytoskeleton), as well as by environmental scanning …

Responses of retinal arterioles and ciliary arteries in pigs with acute respiratory distress syndrome (ARDS)

Abstract Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute lung failure in critically sick patients, which severely compromises the function of multiple organs, including the brain. Although, the optic nerve and the retina are a part of the central nervous system, the effects of ARDS on these ocular structures are completely unknown. Thus, the major goal of this study was to test the hypothesis that ARDS affects vascular function in the eye. ARDS was induced in anesthetized pigs by intratracheal injection of lipopolysaccharide (LPS). Sham-treated animals served as controls. Pigs were monitored for 8 h and then sacrificed. Subsequently, retinal arterioles and short p…

Visualization of corneal vascularization in peripheral hypertrophic subepithelial corneal opacification with OCT angiography.

Purpose The major goal of this study was to test the hypothesis that in patients with peripheral hypertrophic subepithelial corneal opacification (PHSCO), visualization of corneal vessels is better with optical coherence tomography angiography (OCTA) than with conventional slit lamp microphotography. Methods Patients with PHSCO were included in this prospective study. The corneal findings were photographed using a slit lamp camera (Haag Streit BM 900® ) and visualized with anterior-segment OCT (Optovue XR Avanti, Fremont, California, USA). Additionally, OCTA with the Angiovue Imaging™ System was performed in the area of PHSCO. Results Thirty-four eyes of 19 patients (26% male and 74% female…

Sonne, Mond und Sterne

Cholinergic Responses of Ophthalmic Arteries in M3and M5Muscarinic Acetylcholine Receptor Knockout Mice

PURPOSE. To determine the functional role of M 3 and M 5 muscarinic acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice. METHODS. Muscarinic receptor gene expression was quantified in murine ophthalmic arteries using real-time PCR. To test the functional relevance of M 3 and M 5 receptors, ophthalmic arteries from mice deficient in either subtype (M3R -/- , M5R -/- , respectively) and wild-type controls were isolated, cannulated with micropipettes, and pressurized. Changes in luminal vessel diameter in response to muscarinic and nonmuscarinic receptor agonists were measured by video microscopy. RESULTS. With the use of real-time PCR, all five muscarinic receptor …

Analysis of the Corneal Anterior and Posterior Surface in Patients With Peripheral Hypertrophic Subepithelial Corneal Opacification

PURPOSE To characterize the corneal changes in peripheral hypertrophic subepithelial corneal opacification (PHSCO) considering elevation of the anterior and posterior corneal surface, corneal astigmatism, tear secretion, and endothelial cell density. METHODS Thirty-eight eyes of 22 patients with PHSCO on at least 1 eye and 38 eyes of 22 age- and sex-matched healthy subjects were included in this retrospective cross-sectional study. Using the Pentacam system (Oculus, Wetzlar, Germany), measurement of the anterior and posterior corneal surface was performed. In addition, the Schirmer test was conducted, and endothelial cells were counted in the central cornea with a specular microscope (SP-30…

Uncoupling of Endothelial Nitric Oxide Synthase in Perivascular Adipose Tissue of Diet-Induced Obese Mice

Objective— The present study was conducted to investigate the contribution of perivascular adipose tissue (PVAT) to vascular dysfunction in a mouse model of diet-induced obesity. Approach and Results— Obesity was induced in male C57BL/6J mice with a high-fat diet for 20 weeks, and vascular function was studied with myograph. In PVAT-free aortas isolated from obese mice, the endothelium-dependent, nitric oxide–mediated vasodilator response to acetylcholine remained normal. In contrast, a clear reduction in the vasodilator response to acetylcholine was observed in aortas from obese mice when PVAT was left in place. Adipocytes in PVAT were clearly positive in endothelial nitric oxide synthase…

Sample Preparation for Mass-spectrometry-based Proteomics Analysis of Ocular Microvessels

The use of isolated ocular blood vessels in vitro to decipher the pathophysiological state of the eye using advanced technological approaches has greatly expanded our understanding of certain diseases. Mass spectrometry (MS)-based proteomics has emerged as a powerful tool to unravel alterations in the molecular mechanisms and protein signaling pathways in the vascular beds in health and disease. However, sample preparation steps prior to MS analyses are crucial to obtain reproducible results and in-depth elucidation of the complex proteome. This is particularly important for preparation of ocular microvessels, where the amount of sample available for analyses is often limited and thus, pose…

Management of Descemet's membrane haemorrhage after canaloplasty

How to Predict the Suitability for Corneal Donorship?

Background: In Germany, more than one-third of donor corneas harvested are not suitable for transplantation. We evaluated the factors associated with the usability of donor corneas. Method: Data from 2032 consecutive donor corneas harvested at the Rhineland-Palatinate Eye Bank in Mainz, Germany, were retrospectively analyzed. Factors of interest were age, sex, lens status, cause of death, cardiopulmonary resuscitation (CPR), death-to-explantation-interval (DEI), and the influence of these factors on the proportion of discarded donor corneas. Factors associated with endothelial cell density (ECD) were analyzed in a linear regression mixed model. Results: Higher donor age, male gender, pseudo…

Urrets-Zavalia Syndrome After Combined Trabeculotomy-Trabeculectomy Surgery

We report a case of a rare complication after trabeculotomy combined with a small trabeculectomy with mitomycin C in a young patient with juvenile glaucoma. The patient underwent uneventful surgery. However, postoperatively, he experienced a long-lasting hypotony with the need of 2 revision surgeries and 2 short episodes of high-intraocular pressure. He developed a fixed dilated pupil over time.

Allogenic simple limbal epithelial transplantation (alloSLET) from cadaveric donor eyes in patients with persistent corneal epithelial defects

Background/aimTo describe the clinical outcome of allogenic simple limbal epithelial transplantation (alloSLET) utilising tissue from cadaveric donor eyes after failed re-epithelialisation of the corneal surface.MethodsMedical records of 14 eyes from 14 patients treated for persistent corneal epithelial defects with alloSLET were reviewed. The primary outcome measure was complete epithelialisation of the corneal surface. Secondary outcome measures were best corrected visual acuity (BCVA) and postoperative side effects due to surgery or medical therapy.ResultsOf the 14 eyes, 7 received alloSLET only and 7 alloSLET together with penetrating keratoplasty (PK). Thirteen (92.9%) of 14 eyes had a…

The α1B-adrenoceptor subtype mediates adrenergic vasoconstriction in mouse retinal arterioles with damaged endothelium

Background and Purpose The α1-adrenoceptor family plays a critical role in regulating ocular perfusion by mediating responses to catecholamines. The purpose of the present study was to determine the contribution of individual α1-adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene-targeted mice deficient in one of the three adrenoceptor subtypes (α1A-AR−/−, α1B-AR−/− and α1D-AR−/− respectively). Experimental Approach Using real-time PCR, mRNA expression for individual α1-adrenoceptor subtypes was determined in murine retinal arterioles. To assess the functional relevance of the three α1-adrenoceptor subtypes for mediating vascular responses, retinal vascular…

Contribution of nitric oxide synthase isoforms to cholinergic vasodilation in murine retinal arterioles.

Abstract Nitric oxide synthases (NOSs) are critically involved in regulation of ocular perfusion. However, the contribution of the individual NOS isoforms to vascular responses is unknown in the retina. Because some previous findings suggested an involvement of inducible nitric oxide synthase (iNOS) in the regulation of retinal vascular tone, a major goal of the present study was to examine the hypothesis that iNOS is involved in mediating cholinergic vasodilation responses of murine retinal arterioles. Another subject of this study was to test the contribution of the other two NOS isoforms, neuronal (nNOS) and endothelial NOS (eNOS), to cholinergic retinal arteriole responses. Expression o…

Role of  1-Adrenoceptor Subtypes in Pupil Dilation Studied With Gene-Targeted Mice

PURPOSE The α₁A-adrenoceptor (α₁A-AR) subtype was suggested to mediate contraction and trophic effects in the iris dilator muscle, and thus its pharmacological blockade may be involved in intraoperative floppy iris syndrome. We tested the hypothesis that the α₁A-AR mediates pupil dilation and trophic effects in the mouse iris. METHODS The α₁-AR subtype mRNA expression was quantified in iris tissue by real-time PCR. To assess the role of individual α₁-ARs for mediating pupil dilation, the α₁-AR agonist phenylephrine was topically applied to the ocular surface of mice deficient in one of the three α₁-AR subtypes (α₁A-AR(-/-), α₁B-AR(-/-), α₁D-AR(-/-), respectively) and wild-type controls. Cha…

Role of nitric oxide synthase isoforms for ophthalmic artery reactivity in mice.

Abstract Nitric oxide synthases (NOS) are involved in regulation of ocular vascular tone and blood flow. While endothelial NOS (eNOS) has recently been shown to mediate endothelium-dependent vasodilation in mouse retinal arterioles, the contribution of individual NOS isoforms to vascular responses is unknown in the retrobulbar vasculature. Moreover, it is unknown whether the lack of a single NOS isoform affects neuron survival in the retina. Thus, the goal of the present study was to examine the hypothesis that the lack of individual nitric oxide synthase (NOS) isoforms affects the reactivity of mouse ophthalmic arteries and neuron density in the retinal ganglion cell (RGC) layer. Mice defi…

Corneal Epithelial Stem Cells-Physiology, Pathophysiology and Therapeutic Options.

In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia…

Paraproteinämische Keratopathie als klinisches Zeichen einer monoklonalen Gammopathie

ZusammenfassungPatienten mit monoklonaler Gammopathie können eine behandlungsbedürftige paraproteinämische Keratopathie (PPK) aufweisen. Die PPK muss gegenüber verschiedenen Formen von Hornhautdystrophie, einzelnen systemischen Stoffwechselstörungen mit Hornhautbeteiligung sowie gegenüber immunologischen und inflammatorischen Hornhauterkrankungen abgegrenzt werden.

Maggot therapy following orbital exenteration

Orbital exenteration is a radical surgery reserved for the treatment of locally invasive or potentially life-threatening orbital tumours.1 Complications occur after 20–25% of exenterations and include tissue necrosis (6%) and infection (3–4%).2–4 In the present report, we describe the management of a post-exenteration orbital infection by the use of maggots. An 82-year-old multimorbid man presented with a fist-sized painless tumour of the left orbit (fig 1A). Computed tomography demonstrated an orbital mass clearly demarcated from the surrounding tissue (fig 1B). After biopsy, the neoplasm was classified as a borderline-malignant extrapleural solitary fibrous tumour. Therefore, a total orbi…

Retinal arteriole reactivity in mice lacking the endothelial nitric oxide synthase (eNOS) gene

Dysfunctional vascular endothelial nitric oxide synthase (eNOS) has been proposed to play a main pathophysiological role in various ocular diseases. The aim of the present study was to test the hypothesis that the chronic lack of eNOS impairs endothelium-dependent vasodilation in retinal arterioles. The relevance of eNOS for mediating vascular responses was studied in retinal vascular preparations from eNOS-deficient mice (eNOS-/-) and wild-type controls in vitro. Changes in luminal diameter in response to vasoactive agents were measured by videomicroscopy. The thromboxane mimetic, U46619, induced similar concentration-dependent constriction of retinal arterioles in eNOS-/- and wild-type mi…

Aged Mice Devoid of the M3 Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease

The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M1–M5) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M3 receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M3 receptor (M3R−/−). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmenta…

Role of M1, M3, and M5 muscarinic acetylcholine receptors in cholinergic dilation of small arteries studied with gene-targeted mice

Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of vasorelaxing agents from the endothelium. The purpose of the present study was to determine the role of M1, M3, and M5 muscarinic acetylcholine receptors in vasodilation of small arteries using gene-targeted mice deficient in either of the three receptor subtypes (M1R−/−, M3R−/−, or M5R−/− mice, respectively). Muscarinic receptor gene expression was determined in murine cutaneous, skeletal muscle, and renal interlobar arteries using real-time PCR. Moreover, respective arteries from M1R−/−, M3R−/−, M5R−/−, and wild-type mice were isolated, cannulated with mic…