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Chronically elevated circulating fatty acid levels promote lipid accumulation in nonadipose tissues and cause lipotoxicity. Adipose triglyceride lipase (ATGL) critically determines the release of fatty acids from white adipose tissue, and accumulating evidence suggests that inactivation of ATGL has beneficial effects on lipotoxicity-driven disorders including insulin resistance, steatohepatitis, and heart disease, classifying ATGL as a promising drug target. Here, we report on the development and biological characterization of the first small-molecule inhibitor of human ATGL. This inhibitor, designated NG-497, selectively inactivates human and nonhuman primate ATGL but not structurally and functionally related lipid hydrolases. We demonstrate that NG-497 abolishes lipolysis in human adipocytes in a dose-dependent and reversible manner. The combined analysis of mouse- and human-selective inhibitors, chimeric ATGL proteins, and homology models revealed detailed insights into enzyme-inhibitor interactions. NG-497 binds ATGL within a hydrophobic cavity near the active site. Therein, three amino acid residues determine inhibitor efficacy and species selectivity and thus provide the molecular scaffold for selective inhibition.

Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy., Pajed et al. investigate the role of adipocyte hormone-sensitive lipase (HSL) in whole body energy homeostasis. They show that adipocyte-specific HSL Knockout (AHKO) mice fed high fat diet develop fatty liver. Interestingly, this phenotype reverses in aged AHKO mice, possibly due to blunted lipolytic activity in adipose tissue with pronounced lipodystrophy.

The skin is in daily contact with environmental pollutants, but the long-term effects of such exposure remain underinvestigated. Many of these toxins bind and activate the pregnane X receptor (PXR), a ligand-activated transcription factor that regulates genes central to xenobiotic metabolism. The objective of this work was to investigate the effect of constitutive activation of PXR in the basal layer of the skin to mimic repeated skin exposure to noxious molecules. We designed a transgenic mouse model that overexpresses the human PXR gene linked to the herpes simplex VP16 domain under the control of the keratin 14 promoter. We show that transgenic mice display increased transepidermal water loss and elevated skin pH, abnormal stratum corneum lipids, focal epidermal hyperplasia, activated keratinocytes expressing more thymic stromal lymphopoietin, a T helper type 2/T helper type 17 skin immune response, and increased serum IgE. Furthermore, the cutaneous barrier dysfunction precedes development of the T helper type 2/T helper type 17 inflammation in transgenic mice, thereby mirroring the time course of atopic dermatitis development in humans. Moreover, further experiments suggest increased PXR signaling in the skin of patients with atopic dermatitis when compared with healthy skin. Thus, PXR activation by environmental pollutants may compromise epidermal barrier function and favor an immune response resembling atopic dermatitis.

Mutations in the genes coding for patatin-like phospholipase domain-containing 1 (PNPLA1) and α/β-hydrolase domain-containing 5 (ABHD5), also known as comparative gene identification 58, are causative for ichthyosis, a severe skin barrier disorder. Individuals with mutations in either of these genes show a defect in epidermal ω-O-acylceramide (AcylCer) biosynthesis, suggesting that PNPLA1 and ABHD5 act in the same metabolic pathway. In this report, we identified ABHD5 as a coactivator of PNPLA1 that stimulates the esterification of ω-hydroxy ceramides with linoleic acid for AcylCer biosynthesis. ABHD5 interacts with PNPLA1 and recruits the enzyme to its putative triacylglycerol substrate onto cytosolic lipid droplets. Conversely, alleles of ABHD5 carrying point mutations associated with ichthyosis in humans failed to accelerate PNPLA1-mediated AcylCer biosynthesis. Our findings establish an important biochemical function of ABHD5 in interacting with PNPLA1 to synthesize crucial epidermal lipids, emphasizing the significance of these proteins in the formation of a functional skin permeability barrier.

Hintergrund Die vorliegende Studie untersucht aktuelle, im Handel erhaltliche Leseproben in Bezug auf deren Schriftgrosen, logarithmischer Abstufung und Standardisierung der Pruftexte.

Aim Current recommendations regarding the triage of patients with acute diverticulitis for inpatient or outpatient treatment are vague. We hypothesized that a significant number of patients treated as an inpatient could be managed as an outpatient. Method A retrospective cohort study was carried out of 639 patients admitted for a first episode of diverticulitis. The diagnosis of acute diverticulitis was confirmed by computed tomography (CT). The endpoints included length of stay, need for surgery, percutaneous drainage and mortality. Patients were considered to have had a minimal hospitalization, defined as survival to discharge without needing a procedure, hospitalization of ≤ 3 days and no readmission for diverticulitis within 30 days after discharge. Results Of 639 patients, 368 (57.6%) had a minimal hospitalization. Female gender and CT scan findings of free air/fluid were negatively associated with the likelihood of minimal hospitalization. The presence of an abscess

Adipocyte plasma membrane–associated protein (APMAP) has been described as an adipogenic factor in 3T3-L1 cells with unknown biochemical function; we therefore aimed to investigate the physiologic function of APMAP in vivo. We generated Apmap-knockout mice and challenged them with an obesogenic diet to investigate their metabolic phenotype. We identified a novel truncated adipocyte-specific isoform of APMAP in mice that is produced by alternative transcription. Mice lacking the full-length APMAP protein, the only isoform that is expressed in humans, have an improved metabolic phenotype upon diet-induced obesity, indicated by enhanced insulin sensitivity, preserved glucose tolerance, increased respiratory exchange ratio, decreased inflammatory marker gene expression, and reduced adipocyte size. At the molecular level, APMAP interacts with the extracellular collagen cross-linking matrix proteins lysyl oxidase–like 1 and 3. On a high-fat diet, the expression of lysyl oxidase–like 1 and 3 is strongly decreased in Apmap-knockout mice, paralleled by reduced expression of profibrotic collagens and total collagen content in epididymal white adipose tissue, indicating decreased fibrotic potential. Together, our data suggest that APMAP is a novel regulator of extracellular matrix components, and establish that APMAP is a potential target to mitigate obesity-associated insulin resistance.—Pessentheiner, A. R., Huber, K., Pelzmann, H. J., Prokesch, A., Radner, F. P. W., Wolinski, H., Lindroos-Christensen, J., Hoefler, G., Rülicke, T., Birner-Gruenberger, R., Bilban, M., Bogner-Strauss, J. G. APMAP interacts with lysyl oxidase–like proteins, and disruption of Apmap leads to beneficial visceral adipose tissue expansion.

A new generation of logarithmic reading charts has sparked interest in standardized reading performance analyses. Such reading charts have been developed according to the standards of the International Council of Ophthalmology. The print size progression in these calibrated charts is in accordance with the mathematical background of EN ISO 8596. These reading charts are: the Bailey-Lovie Word Reading Chart, the Colenbrander English Continuous Text Near Vision Cards, the Oculus Reading Probe II, the MNREAD Charts, the SKread Charts, and the RADNER Reading Charts. The test items used for these reading charts differ among the charts and are standardized to various extents. The Bailey-Lovie Charts, MNREAD Charts, SKread Charts, and RADNER Charts are also meant to measure reading speed and allow determination of further reading parameters such as reading acuity, reading speed based on reading acuity, critical print size, reading score, and logMAR/logRAD ratio. Such calibrated reading charts have already provided valuable insights into the reading performance of patients in many research studies. They are available in many languages and thus facilitate international communication about near visual performance. In the present review article, the backgrounds of these modern reading charts are presented, and their different levels of test-item standardization are discussed. Clinical research studies are mentioned, and a discussion about the immoderately high number of reading acuity notations is included. Using the logReading Acuity Determination ([logRAD] = reading acuity equivalent of logMAR) measure for research purposes would give reading acuity its own identity as a standardized reading parameter in ophthalmology.

Mutations in PNPLA1 have been identified as causative for autosomal recessive congenital ichthyosis in humans and dogs. So far, the underlying molecular mechanisms are unknown. In this study, we generated and characterized PNPLA1-deficient mice and found that PNPLA1 is crucial for epidermal sphingolipid synthesis. The absence of functional PNPLA1 in mice impaired the formation of omega-O-acylceramides and led to an accumulation of nonesterified omega-hydroxy-ceramides. As a consequence, PNPLA1-deficient mice lacked a functional corneocyte-bound lipid envelope leading to a severe skin barrier defect and premature death of newborn animals. Functional analyses of differentiated keratinocytes from a patient with mutated PNPLA1 demonstrated an identical defect in omega-O-acylceramide synthesis in human cells, indicating that PNPLA1 function is conserved among mammals and indispensable for normal skin physiology. Notably, topical application of epidermal lipids from wild-type onto Pnpla1-mutant mice promoted rebuilding of the corneocyte-bound lipid envelope, indicating that supplementation of ichthyotic skin with omega-O-acylceramides might be a therapeutic approach for the treatment of skin symptoms in individuals affected by omega-O-acylceramide deficiency.

Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired ω-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for ω-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in ω-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism.

The objective of this article was an analytical review of reading charts with regard to the historical background, printing techniques, print quality and print size.For this study original historical reading charts (Jaeger, Snellen, Nieden and Birkhäuser) were investigated microscopically by measuring the lower case letter sizes (iNexis VMA 2520, Nikon, Tokyo). Calculations were made according to EN ISO 8596 and the recommendations of the International Research Council.In the mid-nineteenth century various reading cards were published; however, at that time it was not possible to print lower case letters according to exactly defined standards. Thus, these reading cards were not comparable to each other or between different language versions. At a reading distance of 32 cm Jaeger No. 1 represented in the original edition (1856) a visual acuity of 0.72 and 0.63 in the version from 1945 and the smallest print size of the Snellen reading test (1862) represented 0.55. Nieden No. 1 (1882) corresponded to a visual acuity of 0.59 and the smallest print size of the Birkhäuser cards (1911) 1.5. In the case of all reading cards except the original Birkhäuser cards, there was no logarithmic progression of the print sizes and the sizes of numbers were also not in accordance with the corresponding letter sizes.Print sizes of historical reading charts do not adhere to current standards and were usually not logarithmically scaled. These deficits and the lack of comparability between the historical reading charts may have caused reading cards to be currently underestimated as an accurate diagnostic tool. Nevertheless, the historical reading charts were the successful forerunners of developments for modern reading charts.

To analyze currently available reading charts regarding print size, logarithmic print size progression, and the background of test-item standardization.For the present study, the following logarithmically scaled reading charts were investigated using a measuring microscope (iNexis VMA 2520; Nikon, Tokyo): Eschenbach, Zeiss, OCULUS, MNREAD (Minnesota Near Reading Test), Colenbrander, and RADNER. Calculations were made according to EN-ISO 8596 and the International Research Council recommendations.Modern reading charts and cards exhibit a logarithmic progression of print sizes. The RADNER reading charts comprise four different cards with standardized test items (sentence optotypes), a well-defined stop criterion, accurate letter sizes, and a high print quality. Numbers and Landolt rings are also given in the booklet. The OCULUS cards have currently been reissued according to recent standards and also exhibit a high print quality. In addition to letters, numbers, Landolt rings, and examples taken from a timetable and the telephone book, sheet music is also offered. The Colenbrander cards use short sentences of 44 characters, including spaces, and exhibit inaccuracy at smaller letter sizes, as do the MNREAD cards. The MNREAD cards use sentences of 60 characters, including spaces, and have a high print quality.Modern reading charts show that international standards can be achieved with test items similar to optotypes, by using recent technology and developing new concepts of test-item standardization. Accurate print sizes, high print quality, and a logarithmic progression should become the minimum requirements for reading charts and reading cards in ophthalmology.

The anabolism and catabolism of myocardial triacylglycerol (TAG) stores are important processes for normal cardiac function. TAG synthesis detoxifies and stockpiles fatty acids to prevent lipotoxicity, whereas TAG hydrolysis (lipolysis) remobilizes fatty acids from endogenous storage pools as energy substrates, signaling molecules, or precursors for complex lipids. This study focused on the role of G0/G1 switch 2 (G0S2) protein, which was previously shown to inhibit the principal TAG hydrolase adipose triglyceride lipase (ATGL), in the regulation of cardiac lipolysis. Using wild-type and mutant mice, we show the following: (i) G0S2 is expressed in the heart and regulated by the nutritional status with highest expression levels after re-feeding. (ii) Cardiac-specific overexpression of G0S2 inhibits cardiac lipolysis by direct protein-protein interaction with ATGL. This leads to severe cardiac steatosis. The steatotic hearts caused by G0S2 overexpression are less prone to fibrotic remodeling or cardiac dysfunction than hearts with a lipolytic defect due to ATGL deficiency. (iii) Conversely to the phenotype of transgenic mice, G0S2 deficiency results in a de-repression of cardiac lipolysis and decreased cardiac TAG content. We conclude that G0S2 acts as a potent ATGL inhibitor in the heart modulating cardiac substrate utilization by regulating cardiac lipolysis.

Background and Purpose Monoglyceride lipase (MGL) degrades 2-arachidonoyl glycerol (2-AG), an endogenous agonist of cannabinoid receptors (CB1/2). Because the CB1 receptor is involved in the control of gut function, we investigated the effects of pharmacological inhibition and genetic deletion of MGL on intestinal motility. Furthermore, we determined whether defective 2-AG degradation affects μ-opioid receptor (μ receptor) signalling, a parallel pathway regulating gut motility. Experimental Approach Gut motility was investigated by monitoring Evans Blue transit and colonic bead propulsion in response to MGL inhibition and CB1 receptor or μ receptor stimulation. Ileal contractility was investigated by electrical field stimulation. CB1 receptor expression in ileum and colon was assessed by immunohistochemical analyses. Key Results Pharmacological inhibition of MGL slowed down whole gut transit in a CB1 receptor-dependent manner. Conversely, genetic deletion of MGL did not affect gut transit despite increased 2-AG levels. Notably, MGL deficiency caused complete insensitivity to CB1 receptor agonist-mediated inhibition of whole gut transit and ileal contractility suggesting local desensitization of CB1 receptors. Accordingly, immunohistochemical analyses of myenteric ganglia of MGL-deficient mice revealed that CB1 receptors were trapped in endocytic vesicles. Finally, MGL-deficient mice displayed accelerated colonic propulsion and were hypersensitive to μ receptor agonist-mediated inhibition of colonic motility. This phenotype was reproduced by chronic pharmacological inhibition of MGL. Conclusion and Implications Constantly elevated 2-AG levels induce severe desensitization of intestinal CB1 receptors and increased sensitivity to μ receptor-mediated inhibition of colonic motility. These changes should be considered when cannabinoid-based drugs are used in the therapy of gastrointestinal diseases.

Graphical abstract, Background & Aims Adipose tissue (AT)-derived fatty acids (FAs) are utilized for hepatic triacylglycerol (TG) generation upon fasting. However, their potential impact as signaling molecules is not established. Herein we examined the role of exogenous AT-derived FAs in the regulation of hepatic gene expression by investigating mice with a defect in AT-derived FA supply to the liver. Methods Plasma FA levels, tissue TG hydrolytic activities and lipid content were determined in mice lacking the lipase co-activator comparative gene identification-58 (CGI-58) selectively in AT (CGI-58-ATko) applying standard protocols. Hepatic expression of lipases, FA oxidative genes, transcription factors, ER stress markers, hormones and cytokines were determined by qRT-PCR, Western blotting and ELISA. Results Impaired AT-derived FA supply upon fasting of CGI-58-ATko mice causes a marked defect in liver PPARα-signaling and nuclear CREBH translocation. This severely reduced the expression of respective target genes such as the ATGL inhibitor G0/G1 switch gene-2 (G0S2) and the endocrine metabolic regulator FGF21. These changes could be reversed by lipid administration and raising plasma FA levels. Impaired AT-lipolysis failed to induce hepatic G0S2 expression in fasted CGI-58-ATko mice leading to enhanced ATGL-mediated TG-breakdown strongly reducing hepatic TG deposition. On high fat diet, impaired AT-lipolysis counteracts hepatic TG accumulation and liver stress linked to improved systemic insulin sensitivity. Conclusions AT-derived FAs are a critical regulator of hepatic fasting gene expression required for the induction of G0S2-expression in the liver to control hepatic TG-breakdown. Interfering with AT-lipolysis or hepatic G0S2 expression represents an effective strategy for the treatment of hepatic steatosis.

To develop 28 short sentence optotypes for the English version of the Radner Reading Charts that are as comparable as possible in number and length of words, as well as in difficulty and syntactical construction. Thirty-four English sentences were constructed following the method used for other Radner Reading Charts to obtain “sentence optotypes” with comparable structure and the same lexical and grammatical difficulty. Best comparable sentences were statistically selected and standardized in 50 volunteers. Reading speed and the number of errors were determined. Validity was analyzed with a 124-word long 4th-grade paragraph of the Florida Comprehensive Assessment Test®. Computerized measurements of reading parameters were performed with the RADNER Reading Device (RAD-RD©; in conjunction with a PC and microphone). The mean reading speed obtained with the 28 selected short sentences was 201.53 ± 35.88 words per minute (wpm), as compared to 215.01 ± 30.37 wpm for the long paragraph. The mean reading times were 4.30 ± 0.79 s and 35.26 ± 4.85 s, respectively. The mean number of reading errors was 0.11 ± 0.34. The correlation between the short sentences and the long paragraph was high (r = 0.76; p

In in vitro and in vivo studies, episclerally sutured radio-opaque markers were evaluated as localizers for better determination of the clinical tumour volume prior to stereotactic radio-therapy of uveal melanoma. Four different types of markers were studied in vitro: tantalum marker, 2.5 mm in diameter; ring-shaped markers custom-designed in polymethyl methacrylate (PMMA), 2.6 mm and 3.0 mm in diameter; and barium-impregnated silicone rubber spheres, 2 mm in diameter. In vivo PMMA markers 3.0 mm in diameter and barium-impregnated silicone rubber spheres 2 mm in diameter were used. The best results were obtained with the barium-impregnated silicone rubber spheres both in vitro and in vivo. For the CT-delineation of selected uveal melanomas with either a flat discoid shape or flat tumour extensions or when adjacent serous retinal detachment is present, small episclerally sutured barium-impregnated silicone rubber spheres are useful as localizers for determining the clinical tumour volume.

Durch die Entwicklung der „Clear-Cornea-Incision“ (CCI) konnte bei Kataraktoperationen das Gewebetrauma am Auge reduziert und somit eine schnelle visuelle Rehabilitation erreicht werden. Fur die CCI stehen unterschiedlich geschliffene Inzisionslanzen verschiedener Breiten zur Verfugung. Es ist jedoch bekannt, wie sich unterschiedliche Inzisionsbreiten auf das Hornhautgewebe bei Implantation einer faltbaren Intraokularlinse (IOL) auswirken. Daher untersuchten wir dies mittels Licht-(LM) und Rasterelektronenmikroskopie (REM).

Die Pathogenese des Keratokonus ist bis heute nicht geklart. So findet sich neben einer normalen Verteilung der Kollagentypen auch eine normale posttranslationale Modifikation des Kollagens. Biochemische Untersuchungen weisen beim Keratokonus jedoch auf Veranderungen der Grundsubstanz hin. Zudem unterscheidet sich das biomechanische Verhalten gegenuber Zug-, Druck- und Scherkraften von jenem der normalen Hornhaut.

A thorough understanding of intraocular pressure homeostasis is the biological foundation for the development of new strategies to treat patients with elevated intraocular pressure or glaucoma. However, investigations on the physiology of intraocular pressure homeostasis are also important to gain more comprehensive insights into the pathogenesis of glaucoma and other diseases with associated alterations of intraocular pressure. The present review intends to give alternative insights into the biological and physical aspects of intraocular pressure regulation. The pressure-volume as well as the hydraulic model of intraocular pressure and also the relationship between ciliary blood flow and aqueous humor production, which has moved into the centre of interest because of its possible clinical relevance for glaucoma patients, will be explained. The authors Have attempted to interrelate the different aspects of intraocular pressure genesis and regulation in a comprehensive but understandable way.

Bei schwerst sehbehinderten Kindern sind ubliche Methoden zur Bestimmung des Sehvermogens oft nicht durchfuhrbar. Die vorliegende Arbeit beschreibt ein an unserem Hause in Zusammenarbeit mit der Firma „Techsoft“ entwickeltes Computersystem. Dieses dient der Diagnose des Sehvermogens sowie der Therapieunterstutzung bei Kindern mit visuellen Wahrnehmungsstorungen. Fur die Diagnose stehen verschiedene Testprogramme zur Verfugung: Stehende Streifen, bewegte Streifen, geometrische Objekte unterschiedlicher Grose, Form und Farbe, Preferential-Looking und Konturenbilder, wie das Mondgesicht. Der Computer ermoglicht die Anderung fast jedes einzelnen Testparameters, sowie eine Verknupfung der verschiedenen Testprogramme. Durch Abspeichern eines an die Moglichkeiten der Kinder angepasten Therapieprogrammes kann das Computersystem auch therapeutisch eingesetzt werden. Eine spezielle Tastatur ermoglicht es dem Kind aktiv in den Therapieablauf einzugreifen. Mit diesem Computersystem last sich das Sehvermogen auch bei schwerst sehbehinderten Kindern definiert und reproduzierbar dokumentieren. Wir erhoffen uns davon einen gunstigen Therapieeffekt, weil durch eine umfassende Diagnose, als standiger Begleiter der Therapie, die Kinder gezielter gefordert werden konnen. The present paper introduces into a computersystem, which was developed in cooperation with the “Firma Techsoft“. This Computersystem improves diagnosis of visual acuity as well as the therapy in children with an impaired visual perception. For documentation of the visual faculties different testprograms can be used: motionless stripes, moving stripes, geometrical objects of different size and colour, preferential-looking and outline drawings as, e.g., the moon face. The Computersystem makes it possible to change nearly all testparameters and to link testprograms together. In addition, the computer is helpful in therapy. After storage of a therapyprogram fitting to the visual faculties of these children, this program can be used for individual visual stimulation. A special keyboard gives the children the possibility to participate actively in the therapy. Defined and reproducible data about the visual faculties of children with an impaired visual perception can be drawn with this computersystem. To our mind, this should lead to favourable effects on the therapy.

Die dreidimensionale Anordnung der kollagenen Lamellen in der menschlichen Hornhaut ist bis heute nicht restlos geklart. In einer Vorversuchsreihe haben wir eine spezielle Praparationstechnik zur optimalen Darstellung des Kollagens in der Cornea entwickelt und untersuchten mittels Raster- und Transmissionselektronenmikroskopie die Anordnung der subendothelialen Lamellen in verschiedenen Regionen (limbal, parazentral, zentral) der menschlichen Hornhaut. Die kollagenen Lamellen verlaufen nicht nur in einer Ebene, sondern erreichen, indem sie sich aufteilen und durchkreuzen, auch benachbarte Hornhautschichten. Die Teilungswinkel der Lamellen betragen in der gesamten Cornea etwa 25 °. Auffallig ist, das die Kreuzungswinkel in den verschiedenen Regionen unterschiedlich sind. Sie betragen in der limbalen Region durchschnittlich 25 °; parazentral und zentral variieren sie zwischen 40° und 75°. Eine limbusparallele Hauptverlaufsrichtung last sich fur die limbale und parazentrale Region ermitteln. The discussion about the three-dimensional arrangement of collagen lamellae in the human cornea is equivocal. In the present study we investigated the limbal, paracentral and central region of the posterior layer of human corneal stroma by scanning and transmission electron microscopy. In all regions lamellae split into branches at angles of about 25 ° and are interlaced by crossing each other. By doing so lamellae reach different layers. In all regions we found splitting angles of about 25 °. However, different angles of criss-crossing were found — in the limbal region of about 25 °; in the paracentral and central cornea the angles vary between 40 ° and 75 °. In the limbal and paracentral region we could demonstrate a main course of the lamellae which is parallel to the limbus.

Die Photokoagulation als Therapie eines diabetischen Makulaodems ist seit langer Zeit etabliert. Nach den Studien der ETDRS wird diese Behandlung bei Augen mit einem Visus von mindestens 0,1 oder besser empfohlen. Diese Pilotstudie untersucht die Ergebnisse einer Laserbehandlung bei Augen mit diabetischen CSME und einem Visus von 0,1 und darunter. 46 Patienten (57 Augen) wurden nach Diabetestyp, Diabetesdauer, HbA1C-Status, internistischer Therapie, Nuchternblutzucker, Nikotinabusus, Fern- und Nahvisus, Tonometrie, Katarakt und Rubeosis untersucht. Alle wiesen einen Visus von 0,1 oder weniger zu Untersuchungsbeginn auf. Nach den Beurteilungskriterien der „Airlie House Classification“ wurden die Patienten der Lasertherapie zugefuhrt. Ein fokales Makulaodem wurde mit fokal gesetzten Laserspots behandelt, wahrend ein diffuses Makulaodem mit grid Laserbehandlung therapiert wurde. Die Sehscharfemessung erfolgte alle 3–4 Monate uber insgesamt 3 Jahre, um die Entwicklung der Sehscharfe unter Laserwirkung zu beobachten. Unter den 31 Frauen und 15 Mannern war ein Typ-I-Diabetiker. Das Durchschnittsalter betrug 67 Jahre. Bei 49 (86%) Augen war der Visus stabil geblieben. In 2 Fallen (3,5%) sank die Sehscharfe auf einen quantitativen Messwert. 6 (10,5%) Augen erfuhren eine Verbesserung des Visus. Der HbA1C-Wert lag bei den Patienten mit stabilen Visus unter 9,5%, wahrend er bei den beiden mit Visusabnahme uber 11 % oder mehr lag. Bei jenen Augen, die eine Verbesserung nach Laserbehandlung aufwiesen, lag der HbA1C-Wert auffallend unter 8%. Die Laserbehandlung ist bei diabetisch bedingten CSME auch bei sehr geringer Sehleistung erwagungswert. Der Erhalt des Visus bei 0,1 uber einen mehrjahrigen Zeitraum muss als Erfolg gesehen werden. Durch bestmogliche Compliance, und dadurch erzielte Stoffwechseleinstellung, kann der Lasererfolg optimiert und dem Patienten die geringe Sehleistung erhalten werden. Photocoagulation of diabetic macular edema is established for a long time. Although this therapy is suggested by the ETDRS for eyes above vision of 0,1 or better more, this pilot study underlines the effect of laser treatment in eyes with a visual acuity of 0,1 and less. 46 patients (57 eyes) were examined about type nicotine-abusus, distance + near vision, tonometry, cataract and rubeosis. At the begin of the study all patients had a vision about 0,1 of less and all were treated by laser as it is shown by the „Airlie House Classification“. Visual acuity was tested all 3 to 4 months and continued over 3 years to observe the effectivness. Among 31 women and 15 men was one type-I-diabetic. Mean age was 67 years. In 49 (86%) eyes visual acuity was unchanged. In 2 (3,5%) eyes visual acuity reduced to handmovement. In 6 (10,5%) eyes visual acuity increased. In patients with stable vision the HbA1C-value was below 9,5%. Patients with reduced visual acuity had HbA1C-value of 11% or more. In eyes with increased visual acuity after laser treatment the HbA1C-value was remarkable below 8%. Laser treatment in eyes with diabetic macular edema and visual acuity of 0,1 or less is indicated. A visual acuity about 0,1 over years has to be defined as a success. Good bloodglucose-metabolism and compliance of patients are the most important factors for an optimal result of laser treatment and salvation of visual acuity.

A chart for measuring visual acuity is a better functional test than the routine distance visual acuity testing with single optotypes. The characteristics of a good reading chart are: logarithmically diminishing print size, simultaneous measurement of reading acuity and reading speed, and the calculation of one score for reading acuity corrected for the number of reading errors. The original German-language Radner Reading Chart meets all these requirements, and above all emphasizes the principle of 'sentence optotypes' i.e. highly standardized sentences, because sentence complexity also influences reading performance. Sentence optotypes were created in the Dutch language and tested according to Radner's strict principles. The most equally matched sentence optotypes in terms of reading speed and number of reading errors were selected for the introduction and printing of the first Dutch version of the Radner Reading Chart. The Dutch Radner Reading Chart is precise and practical and therefore useful for research and daily practice.

Fur die gezielte visuelle Forderung von schwerst seh- und mehrfachbehinderten Kindern ist neben einer organisch-funktionellen Diagnose (CT, VEP, Fundus-skopie, Skiaskopie, Orthoptik) auch eine Bestimmung des Sehvermogens wunschenswert. Ubliche nonverbale Prufme-thoden stellen jedoch Minimalanforderungen an das visuelle System, die von diesen Kindern oft nicht erbracht werden konnen. Mit unserem Computersystem konnen wir bei schwerst seh- und mehrfachbehinderten Kindern auch dann eine definierte und reproduzierbare Information uber das Sehvermogen erhalten, wenn ubliche Methoden keine sichere Beurteilung zulassen.

Light-elicited retinal ganglion cell (RGC) responses after fetal neural retinal transplantation have not been demonstrated in animal or human subjects blind from outer retinal degeneration, despite apparent morphologic success. This study was designed to test the hypothesis that the functional success of retinal transplantation may be enhanced by using a young host retina (13 days old).At postnatal day (P)13 C3H/HeJ (rd/rd) retinal degenerate mice received a subretinal transplant, in one eye only, of neural retinal tissue isolated from newborn normal C57/BL6J mice. Between 33 and 35 days after transplantation, local electroretinograms (ERGs) and ganglion cell responses were recorded directly from the retinal surface using a differential bipolar surface electrode. Measurements were performed both with and without light stimulation. Similar recordings were also performed in age-matched eyes subjected to sham transplantation, in control eyes that were not subjected to surgery, and in animals eyes that underwent transplantation at 8 weeks of age. After the recordings, the eyes were processed for light and transmission electron microscopy.Three of 10 mice showed bursts of ganglion cell action potentials (ON response only) as well as recordable intraocular ERGs over the transplant in response to 1-second and 200-msec light stimuli. Light-driven ganglion cell responses could not be recorded in areas outside the transplant in all transplant-recipient eyes, age-matched control eyes, and sham-transplantation eyes. Light responses also could not be recorded in animal eyes that received transplants at an older age (8 weeks). Electron microscopic examination confirmed the presence of photoreceptor outer segments in the areas affected by transplantation.This study demonstrates the presence of light-driven ganglion cell responses after subretinal transplantation in a retinal degenerate model. This finding may reflect functional integration of the transplant with the host, but a rescue effect on remaining host photoreceptors cannot be ruled out. The findings suggest, however, that modification of host parameters, such as host age, may be important approaches for improving the functional success of retinal transplantation.

A pilot study of human neural retinal transplantation was undertaken to investigate three major issues: whether a safe surgical procedure could be devised for transplantation of neural retinal tissue into the subretinal space, whether the transplant would be accepted in the subretinal space, and whether an improvement in vision could be achieved.Eight patients with bare light perception (LP) vision due to retinitis pigmentosa (RP) and one patient with bare LP vision due to advanced neovascular age-related macular degeneration (AMD) received subretinal transplants of human fetal retinal microaggregate suspensions without postoperative systemic immunosuppression. The patient with AMD also received a fetal retinal sheet transplant. The ages of the patients ranged from 31 to 94 years (median, 55 years). The pre- and postoperative evaluations included visual function testing, detailed fundus examinations, fundus photography, fluorescein angiography, macular perimetry using a scanning laser ophthalmoscope (SLO), and full field and focal electroretinograms (ERGs).Three of the eight RP patients demonstrated possible improved light sensitivity during the initial months of follow-up. However, visual improvement disappeared between 3 and 13 months of follow-up. After transplantation, no subject showed any changes in the ERG recordings or SLO macular perimetry relative to their preoperative baseline. No patient experienced a retinal detachment, infection, or extensive bleeding. None of the patients developed retinal vasculitis or intraocular inflammation. In one RP patient, fluorescein angiography and fundus photography documented the formation and maturation of new host retinal vessels in the area of the transplant.Transplantation of fetal retinal photoreceptor suspensions into the subretinal space was achieved safely in nine subjects. Although a definite positive effect on visual function could not be demonstrated, the apparent high tolerance for graft tissue is promising for future efforts in the field of neural retinal transplantation.

Reading acuity as well as reading speed are good predictors of everyday visual function. As visual acuity tests are poor predictors of the real-world function, performance-based tests, e.g., reading speed measurements, can be used for the determination of visual function. Thus, a German reading chart was developed in order to evaluate reading acuity as well as reading speed.Print size is defined as the height of a lower case x and progresses logarithmically from one phrase to another (factor: 1.25). Reading acuity is determined in LogRAD (Reading Acuity Determination). 32 short German phrases were created, comparable concerning grammatical difficulty as well as in number (n = 14), length and position of words. The reading speed parameters measured with a stop-watch in 160 persons (aged: Phi = 21a +/- 3.8a) were calculated in words per minute (w/min). Out of the 32 phrases the 24 most similar ones were selected statistically and used for the reading charts (Radner Reading Charts). With these reading charts a reading acuity score (LogRAD-score) can be calculated considering reading errors in words of different length. Reading speed can be determined at the same time. Reading acuity (LogRAD-Score) was measured in 32 normal eyes of 16 students and compared to the angular visual acuity (LogMAR).The mean reading speed of the test persons was 211.8 +/- 34.1 w/min. 24 phrases fulfilled the test item criteria for the reading chart: mean +/- 0.25 x SD. The reliability analyses yielded an overall Cronbach's alpha coefficient of 0.98! The mean visual acuity measured in 32 eyes was -0.115 +/- 0.097 LogMAR and the mean reading acuity score was +0.026 +/- 0.091 LogRAD. The mean difference was +0.104 +/- 0.066 and the correlation between LogMAR and LogRAD was good (r = 0.59).With these reading charts it is for the first time possible to simultaneously determine reading acuity as well as reading speed in German. The high reliability of the 24 phrases and the high correlation between LogMAR and LogRAD leads us to expect a good reproducibility of the reading acuity evaluations. For the "Radner Reading Charts" we have shown that print size is the main reason for changes of reading speed.

Die Faltlinse Collamer CC 4203 VF der Firma STAAR Surgical wird aus einem Copolymerisat von Kollagen aus Schweinesklera und HEMA gewonnen. Vom Design her ist sie eine Plattenhaptiklinse und mit einem Gesamtdurchmesser von 10,8 mm fur die Kapselsackimplantation gedacht. Im Rahmen einer Machbarkeitsstudie wurden zwischen Dezember 1995 und Marz 1996 24 dieser Linsen unilateral implantiert. Alle Linsen wurden durch eine temporale CCI mit einer Breite von 3,0–3,5 mm mittels Injektor implantiert. 15 Patienten erschienen zur Nachuntersuchung im Dezember 1996. Wahrend des Nachbeobachtungszeitraums muste eine Collamerlinse wegen starkerer Dezentrierung und C-Phanomens explantiert werden.

The present case report describes primary orbital immunocytoma (IgM-kappa) mimicking Hodgkin's disease of the diffuse, lymphocyte predominance type by expressing Hodgkin simulating cells as well as Reed-Sternberg simulating cells (both: H-RS cells).The patient (87a; male) was admitted to hospital with increasing left upper eyelid protrusion. Computed tomography revealed an unspecific accumulation of soft tissue within the orbit. A biopsy was taken. Light microscopical sections were stained with PAS, Giemsa and haematoxylin-eosin. Immunohistochemistry was performed following standard procedures.By means of light microscopy, Hodgkin's disease of the diffuse, lymphocyte predominance type was indicated. This initial diagnosis was mainly based on morphological criteria, e.g. the presence of H-RS-like cells. Since staging work-up produced no evidence of systemic disease, immunohistochemistry was performed. It revealed that the misleading cells were H-RS simulating cells. Finally, the diagnosis made was that of immunocytoma (IgM-kappa); stage I EA.The diagnosis of Hodgkin's disease of the diffuse, lymphocyte predominance type is normally based on morphological criteria. However, in very rare cases immunocytomas simulate this variant of Hodgkin's disease by expressing misleading H-RS simulating cells. Thus, immunohistochemical investigations should generally be included in the criteria for the diagnosis of Hodgkin's disease of the diffuse, lymphocyte predominance type. As far as we are aware, primary immunocytoma mimicking this variant of Hodgkin's disease within the orbit has never been reported.

Many retinal diseases can be treated either with laser treatment or with vitreo-retinal surgery. However, in some of these cases a severe visual loss cannot be avoided and visual rehabilitation has to be initiated. Visual rehabilitation is initially performed by fitting low vision aids. With low vision aids the patients ability to read can be restored as well as many other needs of every days life e.g. reading bus numbers, street names, bank notes or letters. In analogy with the higher life expectancy in the middle european countries the incidence of age related maculopathy will increase in the next years. Thus, the need for visual rehabilitation will increase as well.

Extended aggregates of intracellular axonemal derivatives can be seen within the apical cytoplasm of ciliated cells of apparently healthy domestic pigs. Such alterations were observed in 15 out of 20 animals. Complete (9 + 2) or incomplete (8 + 2 - 5 + 2) intracellular axonemes were found which sometimes arose from mature, irregularly arranged kinetosomes. In addition, bundles of single microtubules and microtubular pairs were found. In previous investigations on the ciliated epithelium of different mammals, intracellular axonemes were investigated only under pathological or experimental conditions. Our findings indicate that these alterations also occur in healthy animals. The extended aggregates of intracellular axonemal derivatives are more likely to be due to a failure of ciliary maturation than to a degradation of incorporated mature cilia.