[Testosterone reduces the expression of keratinization-promoting genes in murine Meibomian glands]. / Reduzierung von Testosteron durch Expression Keratinisierung-fördernder Gene in der Meibom-Drüse der Maus.

BACKGROUND: Extensive keratinization appears to play a major role in the dysfunction of the Meibomian gland. This article presents the potential impact of androgens on limiting keratinization in this tissue, thus, contributing to normal Meibomian gland function and a healthy ocular surface. MATERIALS AND METHODS: Orchidectomized mice were systemically treated with either testosterone or placebo for 2 weeks. The mRNA was then extracted from the Meibomian glands and differential gene expression was investigated by microarray hybridization and evaluation with GeneSifter software as well as gene ontology information from the Gene Ontology (GO) Consortium. RESULTS: By z-score calculations, keratinization was the most significantly gene ontology term influenced by testosterone based on down-regulated genes in the mouse Meibomian gland. In particular, under the influence of testosterone the genes coding for small proline-rich protein (Sprr) 2a, Sprr 2b, Sprr 3, keratins 6a and 17 and periplakin were significantly down-regulated, while Sprr 1a and Sprr 2f were significantly up-regulated. CONCLUSIONS: Testosterone down-regulates the expression of genes promoting keratinization in the Meibomian gland. This may help to prevent Meibomian gland dysfunction by limiting excessive keratinization of this tissue and the adjacent lid margins. The findings elucidate, at least in part, the beneficial impact of androgens on Meibomian gland function and thus on th e health of the ocular surface.

[Increased capillary vulnerability in diabetic retinopathy]. / Gesteigerte kapilläre Vulnerabilität bei der diabetischen Retinopathie.

The retinal capillary network is isolated by Cogan and Kuwabara's method. During prolonged trypsinization the capillaries lose their endothelial cells and pericytes and are transformed into cell-free tubes consisting of basement membranes. This occurs earlier in patients with stage I or II retinopathy than in controls with normal carbohydrate metabolism and patients with stage I hypertension. Therefore, the intercellular junctions and the adhesion between endothelial cells and subendothelial basement lamella are more loosely structured in diabetics than normal subjects, and the cells do not resist the tryptic attack as well. The higher capillary vulnerability demonstrated in these experiments contributes to bleeding and exudation. Whether the local loss of cells in the microcirculation of diabetics occurs primarily in vivo or is only unmasked in vitro manifesting pre-existing cellular damage is discussed.

Morphometric analysis of retinal blood vessels in retinopathia diabetica.

A quantitative investigation of the retinal blood vessels was carried out in 80 diabetics and 20 metabolically healthy controls of the same age and sex distribution. The blood vessels were isolated by trypsinization, stained with PAS, and analyzed by light microscopy. After 1-5 years' duration of diabetes mellitus, capillary lesions in the ocular fundus can be seen microscopically in the slides, but not with a stereomicroscope. In the retinae of persons with normal carbohydrate metabolism, capillary defects were found to a far lesser extent; they were also always localized in the periphery of the retina, whereas the diabetic lesions were localized in the retinal center. In the diabetics, both capillary lesions (e.g., loss of pericytes) and damage of the retinal neurons occurred nearly simultaneously and with the same retinal localization. This suggests that the capillary lesions are not the cause of neuronal degeneration but that both events are caused by the same mechanisms of pathogenesis.

The kinetics of phagocytosis of colloidal substances in experimental insulinopenic diabetes.

Because of a reduction in the rate of phagocytosis by the reticuloendothelial system, the removal of large doses of colloids from the blood is much slower in rats with experimentally induced insulinopenic diabetes than in controls having a normal metabolism. This kinetics corresponds to the exponential response reported in the literature for an injected dose exceeding the "critical dose", with phagocytosis being a crucial parameter. In the case of smaller doses of colloids, however, clearance follows a different kinetic pattern which is here formulated mathematically. It is determined largely by the rate of liver blood flow. In this case, it is not possible to obtain statistical evidence of differences between diabetic and normal rats on administration of gold. Colloidal gold and so-called biological ink proved themselves extremely useful for quantitative studies of phagocytosis, whereas indium proved to be unsuitable under the experimental conditions used in these studies.