Biodegradation and Immunological Parameters of Polyurethane-Based Tissue Adhesive in Arterial Microvascular Anastomoses-A Long-Term In Vivo Study.

In microsurgical anastomosis, non-synthetic fibrin-based adhesives have predominantly shown superior properties to synthetic cyanoacrylates, but they have hardly any clinical application. This study aims to investigate the local and systemic effects of synthetically produced biodegradable adhesive VIVO when used in microsurgical anastomosis. VIVO is used in two different anastomosis procedures in the common carotid artery in a rat model: VIVO in addition to a temporary catheter (VIVO TC) and VIVO with a custom-shaped memory nitinol stent (VIVO SM). Conventionally sutured anastomoses serve as controls (C). Tissue response is assessed by in vivo fluorescence imaging and histological examination. The systemic effects of biodegradation are measured using hematologic parameters and serum levels of transaminase activity and lactate dehydrogenase. Finally, the degree of local adhesion of the different anastomotic procedures is evaluated. Fluorescence imaging shows reduced inflammatory blood flow in the VIVO TC group. Histological analysis of the anastomosed vessels also reveals significantly more inflammation in C than in the two adhesive groups. The severity of VIVO adhesions proves acceptable, and no histotoxic effects of VIVO are detected. The data demonstrate that the synthetic tissue adhesive VIVO is a reliable and-compared to sutures-tissue-friendly adhesive for microsurgical anastomoses.

Mechanical strength and hydrostatic testing of VIVO adhesive in sutureless microsurgical anastomoses: an ex vivo study.

Conventional anastomoses with interrupted sutures are challenging and inevitably associated with trauma to the vessel walls. The goal of this study was to evaluate a novel alternative adhesive-based suture-free anastomosis technique that uses an intraluminal stent. Overall, 120 porcine coronary vessels were analyzed in an ex vivo model and were examined for their mechanical (n = 20 per cohort) and hydrostatic strength (n = 20 per cohort). Anastomoses were made using the novel VIVO adhesive with an additional intraluminal nitinol stent and was compared to interrupted suture anastomosis and to native vessels. Sutureless anastomoses withstood pressures 299 ± 4.47 [mmHg] comparable to native vessels. They were performed significantly faster 553.8 ± 82.44 [sec] (p ≤ 0.001) and withstood significantly higher pressures (p ≤ 0.001) than sutured anastomoses. We demonstrate that the adhesive-based anastomosis can also resist unphysiologically high longitudinal tensile forces with a mean of 1.33 [N]. Within the limitations of an in vitro study adhesive-based suture-free anastomosis technique has the biomechanical potential to offer a seamless alternative to sutured anastomosis because of its stability, and faster handling. In vivo animal studies are needed to validate outcomes and confirm safety.

Impact of quality certification of multidisciplinary head and neck tumor centers.

BACKGROUND: Certification of multidisciplinary tumor centers is nowadays seen as the gold standard in modern oncological therapy for optimization and realization of guideline-based therapy and better outcomes. Single cases are reimbursed based on diagnosis-related groups (DRG). We aimed to review efficiency, cost analysis, and profitability following a certification. METHODS: Tumor board certification at the university hospital Aachen was implemented in 2013. We compared 1251 cases of oropharyngeal cancer treated from 2008 to 2017 before and after certification. For this purpose, several patient characteristics, surgery, and stay-related constants, as well as expenses and reimbursement heights were analyzed statistically. RESULTS: Following certification, the total case and patient number, surgery duration, hours of mechanical ventilation, case mix index points, DRG reimbursements as well as the costs increased significantly, whereas days of intensive care unit, amount of blood transfusions, patient clinical complexity level (PCCL) and the overall stay were significantly lowered. No changes were observed for the patient's age and gender distribution. Also, the predetermined stay duration stayed constant. CONCLUSIONS: Certification of head-neck tumor centers causes a concentration of more complex cases requiring higher surgical efforts, which can be processed more efficiently due to a higher level of professionalism. Despite their benefits in cancer care, without compensation, centers may be struggling to cover their expenses in a system, which continuously underestimates them.

Effectiveness of face-to-face, blended and e-learning in teaching the application of local anaesthesia: a randomised study.

BACKGROUND: Local anaesthesia plays a key role in many aspects of a dentist's work. The required skills to perform anaesthesia successfully are acquired at university. To take advantage of the possibilities for new teaching formats, a blended learning concept for the local anaesthesia course was developed. The aim of the study was to compare the effectiveness of face-to-face, blended and e-learning in teaching in local anaesthesia by assessing students' knowledge gain, performance of practical skills and satisfaction with the course. METHODS: All participants (n = 37) were randomly allocated into three groups. After acquiring the theoretical background in the blended learning, e-learning or lecture groups, a test to assess knowledge gain was performed. The performance of the practical skills was assessed in a small-group seminar. Student attitudes were evaluated with a questionnaire. RESULTS: The blended group showed significantly better results (mean = 17, SD =1.5) in theoretical knowledge gain than the other two groups (e-learning group: mean = 14.7, SD = 2.2; lecture group: mean = 14.8, SD =2.3). When comparing the results of the clinical skills assessment, there was no significant difference among all three groups (p > 0.017). The participants confirmed a high overall satisfaction with the course, in particular with the blended learning approach. CONCLUSION: This study indicates that blended learning improves the learning outcome for theoretical knowledge in teaching local anaesthesia more than either face-to-face learning or e-learning alone. Furthermore, the blended learning approach is highly appreciated by the students. For acquiring practical skills, this study shows that blended learning is as effective as other teaching methods.

An innovative PantoDict program for reporting panoramic radiographs using automatic speech recognition in dental education: a randomized observer-blinded study.

OBJECTIVE: The objective of this study was to assess the effect of an e-learning program including automatic speech recognition on outcomes assessment in interpreting panoramic radiographs at a dental school. STUDY DESIGN: For instruction in reporting findings on panoramic radiographs, 36 participants were divided randomly into 3 seminar groups. Group A used the new PantoDict digital e-learning program for training. Group B used both PantoDict and conventional face-to-face classroom instruction. Group C used conventional instruction only. After attending 3 seminars, all students completed an examination on reporting a panoramic radiograph and evaluated the course. RESULTS: Both groups using PantoDict (groups A and B) had significantly higher examination scores than the conventional group (P ≤ .002). However, students in group C were more likely than those in group A to agree that their knowledge and confidence improved following the seminars. Students in group A would have preferred an instructor for the first seminar. The evaluation confirmed that students were satisfied with the e-module regarding usability and didactics. Most students indicated that they would like to use PantoDict all the time. CONCLUSIONS: The e-learning program with automatic speech recognition is a useful device for completing radiology reports and can be used as a complementary tool in face-to-face teaching.

Impact of Wound Closure on the Corrosion Rate of Biodegradable Mg-Ca-Zn Alloys in the Oral Environment.

Magnesium alloys have exhibited a rapid rate of corrosion and thus early implant failure, so this study was designed to investigate the longer-term effects and in particular on wound closure. The aim of the study is to evaluate Mg-Ca-Zn Alloys as promising biodegradable implants in the field of maxillofacial surgery, which have so far never been evaluated for the changing conditions from a saliva to a serum-like environment after wound closure. Magnesium-0.6/calcium-0.8 wt.% zinc alloys were either immersed for 10 days in artificial saliva or 10 days in Hank's salt solution as control groups. The test group was transferred from artificial saliva to Hank's salt solution after 5 days in order to simulate wound closure. Corrosion rates were determined by immersion testing. Additional electron microscopy and energy dispersive X-ray spectroscopy (EDX) were performed. Prior artificial saliva exposure led to significantly decreased (p = 0.0272) corrosion rates after transfer to Hank's solution in comparison to sole Hank's solution exposure (0.1703 vs. 0.6675 mg/(cm2·day)) and sole artificial saliva exposure (0.3180 mg/(cm2·day)), which both exhibit a strong increase after 5 days. The results were in accordance with the scanning electron microscopy and EDX pictures. Prior saliva exposure could protect from increasing corrosion rates after wound closure. Thus Mg-Ca-Zn Alloys are promising future implant alloys in oral surgery, whereas other surgical fields without saliva exposure have to deal with accelerated corrosion rates after 5 days.

Three-dimensional evaluation of the posterior airway space: differences in computed tomography and cone beam computed tomography.

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) becomes increasingly important. For diagnosis and surgery, computed tomography (CT), and cone beam computed tomography (CB-CT) are used equally, although in most of cases, patient positioning differs between supine positioning (CT) and upright seating positioning (CB-CT). We measured volumetric and anatomical changes in the posterior airway space (PAS) between upright and supine positioning in a three-dimensional set up. MATERIALS AND METHODS: Coherent CT and CB-CT scans of 55 patients were included in the study. Using Brainlab ENT 3.0, image data was superimposed, and three-dimensional models were segmented. PAS height, cross-sectional area, vertical and horizontal position of the mandible and hyoid, and volumetric analyses of the three-dimensional models were measured. RESULTS: PAS height and cross-sectional area were significantly higher in CB-CT compared to CT scans (p < 0.001). In the vertical dimension, the mandible and hyoid were localized more caudally in CB-CT in contrast to CT scans (p < 0.04; p < 0.001). Three-dimensional evaluation showed a greater volume of the PAS in CB-CT (p < 0.0001). Pearson correlation coefficient showed a correlation between vertical positioning of the mandible and hyoid compared to the positioning of the patient. CONCLUSIONS: Patient positioning during CT and CB-CT has an effect on the location of anatomical structures like the mandible and hyoid and changes the dimensions and volume of the posterior airway space significantly. CLINICAL RELEVANCE: The radiological technique used and the positioning of the patient should be taken into account when considering further surgical therapy.

Perioperative safety and complications in treatment of oral and maxillofacial surgery patients under general anesthesia with obstructive sleeping disorders.

Patients with sleeping disorders, such as obstructive sleep apnea, (OSA) have a higher risk for postoperative complications after maxillofacial surgery under general anesthesia. The aim of this study was to detect specific complications after oral and maxillofacial surgery. Sixty-nine cases of patients with middle or severe sleep apnea who underwent an operation under general anesthesia in the oral and maxillofacial region were retrospectively analyzed. This group was compared with an age and diagnosis matched group without sleep apnea receiving the same operative treatment. We found a significant difference between the two groups concerning body mass index, the ASA-Index, the Cormack-Mallampati Index, the number of pre-existing conditions, and home medication (p < 0.05). Concerning the length of stay, overrun of estimated mean length of stay, and number of surgical complications and hypertonic events, no difference could be detected. Almost 28% of the patients with OSA in our study suffered a substantial respiratory complication even under intensive care observation. The number of patients with oxygen desaturation was 9% in the control group, which differed significantly (p = 0.0093) from the number of such patients in the OSA group. In this study, we have shown that the presence of OSA in patients undergoing elective maxillofacial surgery is associated with a considerable number of comorbidities in the postoperative period. Through preoperative OSA screening and OSA evaluation, an improvement in management of surveillance resources could be achieved and the OSA-specific risk could be assessed more precisely and also reduced.

Preparation Steps for Measurement of Reactivity in Mouse Retinal Arterioles Ex Vivo.

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 blood vessels, which is ~ ≤ 30 µm in luminal diameter. To circumvent the problem of direct isolation of these retinal microvessels for functional studies, we established an isolation and preparation technique that enables ex vivo studies of mouse retinal vasoactivity under near-physiological conditions. Although the present experimental preparations will specifically refer to the mouse retinal arterioles, this methodology can readily be employed to microvessels from rats.

Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice.

Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an important role in the maintenance of ocular vascular homeostasis. Therefore, perturbations in vascular NO synthesis have been implicated in the pathogenesis of several ocular diseases. We recently reported that eNOS contributes significantly to vasodilation of the mouse ophthalmic artery. Interestingly, dilatory responses were also retained in eNOS gene-deficient mice (eNOS-/-), indicating inherent endothelial adaptive mechanism(s) that act as back-up systems in chronic absence of eNOS to preserve vasorelaxation. Thus, this study endeavoured to identify the compensatory mechanism(s) in the ophthalmic artery of eNOS-/- mice employing isolated arterial segments and pharmacological inhibitors in vitro. Endothelium removal virtually abolished acetylcholine (ACh)-induced vasodilation, suggesting an obligatory involvement of the endothelium in cholinergic control of vascular tone. However, non-NOS and non-cyclooxygenase components compensate for eNOS deficiency via endothelium-derived hyperpolarizing factors (EDHFs). Notably, arachidonic acid-derived metabolites of the 12-lipoxygenase pathway were key mediators in activating the inwardly rectifying potassium channels to compensate for chronic lack of eNOS. Conclusively, endothelium-dependent cholinergic responses of the ophthalmic artery in the eNOS-/- mice are largely preserved and, this vascular bed has the ability to compensate for the loss of normal vasodilator responses solely via EDHFs.

Evaluation of bone resorption in fibula and deep circumflex iliac artery flaps following dental implantation: A three-year follow-up study.

Long-term results of dental implant treatment in fibula free and deep circumflex iliac artery (DCIA) free flaps are scarce. The purpose of this study was to assess and compare peri-implant bone resorption of vascularized bone flaps treated with dental implants. A total of 28 patients, 14 fibula and 14 DCIA flaps, respectively, underwent reconstruction of the lower and upper jaw by the use of vascularized bone flaps and were treated with dental implants. Peri-implant bone resorption was measured using digital panographs up to 3 years. Radiographic pictures were taken immediately after implant surgery before prosthetic rehabilitation (T0), the second after 6-12 months (T1), the third after 13-24 months (T2), and the fourth after 25-36 months (T3). Over a period of 3 years, implant resorption changed significantly over time (pD1 = 0.0113, pD2 = 0.0232, pD3 = 0.0143). However, a significant difference in overall resorption between implants with fibula flaps and DCIA could not be detected for the patient average or within the implant-level analysis. Flaps presented minimal resorption from beneath (mean resorption DCIA 0.65, fibula = 0.26). Strong peri-implant bone resorption changed significantly over time. However, no significant difference was observed between fibula and DCIA flaps.

Fracture patterns after bilateral sagittal split osteotomy of the mandibular ramus according to the Obwegeser/Dal Pont and Hunsuck/Epker modifications.

The aim of this study was to compare the fracture patterns after sagittal split osteotomy according to Obwegeser/Dal Pont (ODP) and Hunsuck/Epker (HE), as well as to investigate the relationship between lateral bone cut ending or angle and the incidence of unfavorable/bad splits. Postoperative cone-beam computed tomograms of 124 splits according to ODP and 60 according to HE were analyzed. ODP led to 75.8% and HE led to 60% lingual fractures with mandibular foramen contact. Horizontal fractures were found in 9.7% and 6.7%, respectively, and unfavorable/bad splits were found in 11.3% and 10%, respectively. The lateral osteotomy angle was 106.22° (SD 12.03)° for bad splits and 106.6° (SD 13.12)° for favorable splits. Correlations were found between favorable fracture patterns and split modifications and between buccal ending of the lateral bone cut and bad splits (p < 0.001). No relationship was observed between split modifications (p = 0.792) or the osteotomy angle (p = 0.937) and the incidence of unfavorable/bad splits. Split modifications had no influence on the incidence of unfavorable/bad splits, but the buccal ending of the lateral bone cut did have an influence. More lingual fractures with mandibular foramen contact are expected with the ODP modification. The osteotomy angle did not differ between favorable and bad splits.

Intraosseous stability of dental implants in free revascularized fibula and iliac crest bone flaps.

The aim of this study was to investigate the influence of two different microvascular reanastomized bone transplants on primary (PS) and secondary stability (SS) of dental implants. Totally 96 implants (Bone Level, Institut Straumann AG, Basel, Switzerland) were inserted in fibula (n = 50) and iliac crest (n = 46) in mean of 97.7 SD 75.6 weeks after performing reconstructive surgery. For measuring PS and SS the resonance frequency (RFA) analysis was used in mesiodistal and vestibulo-oral direction to quantify the implant stability quotient (ISQ). Mean values (ISQ) for PS in fibula was about 79.48 SD 2.41 and in iliac crest 61.10 SD 3.34 as well as SS in fibula was about 75.59 SD 5.10 and in iliac crest 73.63 SD 5.34. Statistically significant differences between both flaps were found for PS in mesiodistal and vestibulooral direction (p < 0.001). Between the primary and SS a significant decrease was recognized in fibula flap (p < 0.01) as well as an increase in iliac crest flap (p < 0.001). Statistically no difference was found between both bone flaps for SS (p = 0.076). The implant stability in fibula and iliac crest flap after osseointegration is similar to each other. Therefore, it is not important for choosing the suitable donor side.

Evaluation of the accuracy of a mobile and a stationary system for three-dimensional facial scanning.

PURPOSE: Numerous three-dimensional (3D) facial scanners have emerged on the market; however, publications evaluating their accuracies are sparse. In this study, the accuracy of two 3D scanners used in facial scanning was evaluated. MATERIALS AND METHODS: A test specimen was attached at the right cheek and the forehead of 41 volunteers. These volunteers were scanned with Artec EVA® and FaceScan3D®. The acquired data were aligned to a 3D model of the test specimen for comparing the mean error, original length and width and angles to the measured values. RESULTS: The mean error in Best Fit alignment is significantly lower using Artec EVA (p < 0.001) for both test specimens. The deviation from the original length and width is significantly lower for the test specimens (p < 0.01) when measured with Artec EVA. The aberration of the angles measured between the front plane and the side plane is significantly lower when measured with Artec EVA (p < 0.001). Captured with Artec EVA the discrepancy between the original angle and the angle measured between the side planes to each other is significantly lower (p < 0.01). CONCLUSIONS: Scanning with Artec EVA leads to more accurate 3D models as compared to scanning with FaceScan3D. The exactness achieved by both scanners is comparable to other scanners mentioned in literature.

The use of mobile 3D scanners in maxillofacial surgery.

There are many possibilities for the use of three-dimensional (3D) scanners in maxillofacial surgery. This study aimed to investigate whether the bundling and syncing of two 3D scanners has advantages over single-scanner acquisition in terms of scan quality and the time required to scan an object. Therefore, the speed and precision of 3D data acquisition with one scanner versus two synced scanners was measured in 30 subjects. This was done by analyzing the results obtained by scanning test objects attached to the forehead and cheeks of the subjects. Statistical methods included the Student t test for paired samples. Single-scanner recording resulted in significantly lower mean error of measurement than synced recording with two scanners for length (P < 0.001), all frontal/lateral plane angles (P = 0.034, P < 0.001, P = 0.002, P = 0.003), and side/side plane angles (P = 0.014, P < 0.001, P = 0.015, P = 0.011) of the test object on the cheek. Likewise, the single-scanner method resulted in a significantly lowermean error of measurement than the two-scanner method for frontal/lower plane angles (P < 0.001), right/lower plane angles (P < 0.001), and left/lower plane angles (P = 0.002). Conversely, synced recording of data with two scanners resulted in a significant reduction of scanning time (P < 0.001). Compared to data acquisition with a single 3D scanner, the bundling of two 3D scanners resulted in faster scanning times but lower scan quality.

Influence of Connecting Two Standalone Mobile Three-Dimensional Scanners on Accuracy Comparing with a Standard Device in Facial Scanning.

OBJECTIVES: In this study is investigated if bundling of two scanners leads to better accuracy in recording faces than a standard face-scanning device. MATERIAL AND METHODS: In a group of 28 volunteers, two test specimens were attached to their faces: one on their forehead and one turned 90° on their cheek. Each volunteer was scanned by FaceScan3D® and two bundled Artec EVA® scanners. The scans were aligned to a three-dimensional model of the test specimen, and the mean error was recorded. Length, width and angles between the test specimen's planes were compared. RESULTS: The mean deviation is significantly lower for the cheek test specimen in alignment (P < 0.001), length and width (P < 0.001) but not for the forehead test specimen in alignment and length and width (P > 0.05) using FaceScan3D®. The aberration from the original angle between two sides of the test specimen is significantly lower measured with Artec EVA® for the angle between the front and the bottom plane of both test specimens (P < 0.01). Besides the angle between the right plane and the bottom plane as well as the top plane of the test specimen mounted to the cheek, the deviation of the angle between the other side planes to each other is significantly lower (P > 0.05) scanned with Artec EVA®. CONCLUSIONS: Compared to FaceScan3D®, two bundled Artec EVA® scanners provide different accuracies depending on the location of the measured parameters. The accuracy measured for both scanners is inside the range found in the literature.

High-Concentration Liquid Prednisolone Formula: Filling a Therapeutic Niche in Severe Acute Attacks of Urticaria and Angioedema.

BACKGROUND/AIMS: According to current guidelines, the emergency kit for patients with severe urticaria and/or angioedema should include a corticosteroid with a prednisolone-equivalent of 50-100 mg. Since severe dysphagia may occur in anaphylaxis, liquid corticosteroids are advantageous. Presently, only liquid preparations with less than 100 mg prednisolone equivalent are available worldwide. METHODS: We prepared a highly concentrated liquid prednisolone formula for oral administration (1 or 5 mg prednisolone per ml). We observed efficacy and safety of 100 mg or >250 mg liquid oral prednisolone in comparison to intravenous administration (250 mg prednisolone) in 53 patients with urticaria and/or angioedema. RESULTS: The symptom control achieved with oral administration was comparable to that obtained with intravenous therapy, with remission of at least 50% of the symptoms in less than 30 min. No side effects occurred during the treatment period. CONCLUSION: The liquid prednisolone formula is an additional therapeutic rescue medication in dermatological emergency medicine, filling a therapeutic niche for patients who need high-concentration liquid prednisolone. It is suitable for self-administration emergency kits in children and adults, in accordance with current guidelines.

Three-Dimensional Evaluation of Implant Bed Preparation and the Influence on Primary Implant Stability After Using 2 Different Surgical Techniques.

PURPOSE: Surgical techniques affect primary implant stability, which is required for osseointegration. The aim of this study was to investigate the influence of full-guided surgery on the dimension of implant site in relation to primary stability. MATERIALS AND METHODS: After implant site preparation in artificial bone by full-guided (FG) or non-guided (NG) workflows to create final diameters of 3.3, 4.1, and 4.8mm and depths of 8 or 12 mm, computed tomograms were obtained and the volume of the osteotomies was analyzed 3 dimensionally. After comparing implant insertions, the implant stability quotient (ISQ) was measured by resonance frequency analysis (RFA). RESULTS: Volume analysis of the implant site showed significant differences (P < .0001) between surgical procedures (FG vs NG) at a depth of 12 mm for all diameters (3.3 mm, 61.98 ± 5.84 vs 80.96 ± 9.65 mm(3); 4.1 mm, 107.45 ± 6.91 vs 132.07 ± 5.16 mm(3); 4.8 mm, 158.62 ± 10.21 vs 182.00 ± 6.25 mm(3)) and at a depth of 8 mm for diameters of 4.1 mm (71.76 ± 8.38 vs 83.64 ± 7.54 mm(3)) and 4.8 mm (103.84 ± 6.73 vs 120.55 ± 14.63 mm(3)). RFA showed significant differences for implants with a diameter of 4.8 mm and lengths of 12 mm (ISQ, 69.3 ± 4.09 for FG vs 65.05 ± 5.61 for NG; P = .0007) and 8 mm (64.5 ± 4.16 for FG vs 58.85 ± 6.72 for NG; P = .0107). CONCLUSIONS: The use of FG implant surgery decreases the bone volume removed during osteotomy preparation, which can lead to greater primary stability.

Effect of the M1 Muscarinic Acetylcholine Receptor on Retinal Neuron Number Studied with Gene-Targeted Mice.

Pharmacological activation of the M1 muscarinic receptor subtype was suggested to promote the survival of retinal neurons. We examined the hypothesis that the M1 receptor is crucial for retinal neuron survival in vivo by using mice devoid of the M1 receptor gene. Muscarinic receptor gene expression was determined in the retina using real-time PCR. The amount of neurons in the retinal ganglion cell layer and of axons in the optic nerve was determined in retinal wholemounts stained with cresyl blue and in optic nerve cross-sections stained with toluidine blue, respectively. mRNA of all five muscarinic receptor subtypes (M1-M5) was detected in the retina from wild-type mice. Remarkably, M2 and M3 receptor mRNA were most abundant. In retinas from M1 receptor-deficient mice, M4 receptor mRNA expression was increased compared to that of wild-type mice, while no marked changes in the mRNA expression levels of the other muscarinic receptor subtypes were observed. The amount of cells in the retinal ganglion cell layer and the amount of axons in the optic nerve did not differ between M1 receptor-deficient and wild-type mice. The present findings suggest that the M1 receptor is not essential for the survival of retinal neurons in vivo.

Role of α1-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. Changes in pupil diameter were measured under a microscope in restrained mice. Moreover, iris and iris muscle thickness were determined in cryosections. RESULTS: Messenger RNA for all three α1-AR subtypes was detected the iris of wild-type mice with a rank order of abundance of α1A ≥ α1B > > α1D. The lack of a single α1-AR gene did not affect mRNA expression of the remaining two receptor subtypes. Phenylephrine induced pupil dilation in wild-type mice that was reduced in extent and duration in α1A-AR(-/-) and, less so, in α1B-AR(-/-) but not in α1D-AR(-/-) mice. The lack of a single α1-AR subtype had no effect on iris or iris muscle thickness. CONCLUSIONS: The α1-AR-induced mydriasis in mice is mediated mainly by the α1A-AR, with a smaller contribution of the α1B-AR, matching the relative abundance of these subtypes at the mRNA level. The lack of a single α1-AR subtype does not appear to cause atrophy in the mouse iris.