Association between atopic dermatitis and autoimmune diseases: a population-based case-control study.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder and is well known to be associated with other atopic conditions. There is increasing evidence for an association also with nonatopic conditions, including autoimmune diseases, but data are limited about several autoimmune diagnoses. OBJECTIVES: To investigate the association between AD and autoimmune diseases. METHODS: This case-control study used Swedish national healthcare registers. The source population comprised the entire Swedish population aged ≥ 15 years from 1968 to 2016. Cases, including all those with an inpatient diagnosis of AD (from 1968) and/or a specialist outpatient diagnosis of AD (from 2001), were matched by sex and age to healthy controls (104 832 cases of AD, 1 022 435 controls). RESULTS: AD was significantly associated with one or more autoimmune diseases compared with controls - adjusted odds ratio (aOR) 1·97, 95% confidence interval (CI) 1·93-2·01 - and this association was significantly stronger in the presence of multiple autoimmune diseases compared with only one. The association was strongest for autoimmune disorders involving the skin (aOR 3·10, 95% CI 3·02-3·18), the gastrointestinal tract (aOR 1·75, 95% CI 1·69-1·82) or connective tissue (aOR 1·50, 95% CI 1·42-1·58). In the overall analysis, men with AD had a stronger association with rheumatoid arthritis and coeliac disease than did women with AD. In subanalyses, the findings remained stable in multivariable analyses after adjustment for smoking and parental autoimmune disease. CONCLUSIONS: This large population-based study indicates significant autoimmune comorbidity of adults with AD, especially between AD and autoimmune dermatological, gastrointestinal and rheumatological diseases. Having multiple autoimmune diseases resulted in a stronger association with AD than having only one autoimmune disease.

Mitochondrial elongation in the macular RPE of aging monkeys, evidence of metabolic stress.

PURPOSE: This study was conducted to determine whether mitochondria of the macular retinal pigment epithelium (RPE) change with age in rhesus monkeys (Macaca mulatta). Mitochondria are the main instigators of oxidative stress, which has often been considered to play a role in the pathogenesis of age-related macular degeneration (AMD). Any pathological changes in the mitochondria of aging macular RPE, the main target of AMD, would be a clue to the pathogenesis of this common retinal degeneration afflicting both monkey and man. METHODS: Transmission electron microscopy was used to identify mitochondria and to determine their appearance, their density per unit area of RPE cytoplasm and their length. The eyes of seven monkeys, 1, 2, 6.5, 23, 26, 27 and 35 years of age, were studied. Measurements were kept separate for the basal, middle and apical third of each cell. The basal third of the macular RPE had many more mitochondria than the middle third, and the apical third was almost devoid of mitochondria. RESULTS: Mitochondrial number decreased and length increased with age. The increase in length was associated with an unusual clustering of mitochondria into parallel arrays of elongated mitochondria, with their long axis orthogonal to the basal membrane of the cell, structures not described before in RPE. CONCLUSIONS: Mitochondrial elongation is associated with metabolic and/or oxidative stress, which implies that age produces stress in macular RPE. The increased clustering of very elongated mitochondria suggests that pathological changes occur in mitochondrial organization with age. These changes support the hypothesis that age-related mitochondrial dysfunction plays a role in the pathogenesis of AMD.

Bestrophin detected in the basal membrane of the retinal epithelium and drusen of monkeys with drusenoid maculopathy.

PURPOSE: To determine if bestrophin is present in the basal membrane of macular retinal pigment epithelium (RPE) and in drusen of rhesus monkeys with age-related drusenoid maculopathy. METHODS: The macular region of three rhesus monkeys (Macaca mulatta), 23-24 years of age, with drusenoid maculopathy was dissected from eyes fixed with 4% paraformaldehyde. The macula was sectioned into rectangular pieces. The sclera was removed from each segment and the remainder separated into segments of neural retina with retinal epithelium or choroid with retinal epithelium. These segments were incubated with a goat polyclonal antibody to human bestrophin 1, reacted with gold-labeled rabbit antibody to goat IgG, silver-enhanced, and processed for transmission electron microscopy. RESULTS: Bestrophin-labeled gold particles were found in quasi-linear arrays on the basal surface of the macular RPE and also within drusen where bestrophin was found in segments of membranous-like material. The array density of the bestrophin-linked gold particles on the basal membrane of the epithelium had a maximal value of about 5-100 bestrophin molecules/micron(2). Immuno-detection of bestrophin was most effective when examined in an RPE layer that remained attached to the neural retina, where the basal surface of the epithelium is more directly exposed to the antibodies. CONCLUSION: Bestrophin is present on the basal membrane of macular RPE of rhesus monkeys with age-related drusenoid maculopathy, and also found in the membranous-like structures of drusen. The latter finding provides insight into the pathogenesis of drusen by indicating that segments of the basal membrane of RPE contribute to the material that accumulates within drusen.

Behavior of retinal epithelium to bleb detachment versus retinectomy.

PURPOSE: To compare the behavior of the retinal pigment epithelium to a bleb detachment versus removal of a segment of neural retina. METHODS: A bleb detachment was performed on 14 adult pigmented rabbits. In seven rabbits, the neural retina was removed within the bleb detachment. The rabbits were followed for months after surgery by scanning laser ophthalmoscopy and post mortem histology using light and electron microscopy. RESULTS: Bleb detachment produces a transformation of the retinal epithelial layer that results in migration, enlargement of cell size and accumulation of large amounts of lysosomal material, resembling that found in Chediak-Higashi syndrome. Retinectomy causes migration of the epithelial cells, development of multiple layers with vacuoles but no accumulation of lysosomal material. CONCLUSION: The neural retina appears to exert a strong influence on the behavior of the retinal epithelial layer. Brief separation of the neural retina from the epithelium provokes a rapid transformation of this cell layer leading to migration of the cells and apparent faulty digestion of phagosomes, causing an enormous buildup of lysosomal debris. Removal of the neural retina also provokes retinal epithelial cell migration but no buildup of lysosomal debris occurs, presumably due to the absence of photoreceptor outer segments and consequently phagosomes. This migratory tendency, which appears to alter lysosomal degradation, could lead to apoptosis of these epithelial cells.

Photoreceptor allografts in a feline model of retinal degeneration.

BACKGROUND: Photoreceptor transplants provide a potential means to restore function in a degenerate retina and/or rescue degenerating host photoreceptors by trophic influences. We have examined photoreceptor allografts in the Abyssinian cat model of hereditary photoreceptor degeneration to determine the viability and influence of such transplants on the host retina. METHODS: Small pieces of 3- to 5-day-old normal kitten retina containing undifferentiated photoreceptors were injected into the subretinal space of adult Abyssinian cats at an early stage of retinal degeneration using standard vitreo-retinal surgical techniques. The retinas were examined by ophthalmoscopy and fundus photography, then by light and electron microscopy at different times after surgery. RESULTS: Such allografts survive for at least 6 months after surgery. The photoreceptors develop outer segments, invariably in rosettes. The transplants gradually integrate with the host retina but detach the host photoreceptor layer from the retinal pigment epithelium (RPE), which tends to reduce the number of host photoreceptors over the transplant. There is no slowing of the photoreceptor degeneration in neighboring non-detached retina. Inflammation or rejection was not detected. CONCLUSION: Undifferentiated, neonatal photoreceptor allografts survive and develop outer segments in the subretinal space of the Abyssinian mutant feline retina. The allografts gradually integrate with the host neural retina without inducing rejection. In the vicinity of the transplant there is increased loss of host photoreceptors, considered to be due to their detachment from the RPE layer. There is no evidence of any rescue of host photoreceptors elsewhere in this mutant retina.

Healon Yellow as a surgical tool in maneuvering intraocular tissues.

Tinted sodium hyaluronate (Healon Yellow) was used during posterior segment surgery mainly for the dissection of epiretinal membranes in cases of proliferative diabetic retinopathy and macular pucker. The yellow color facilitated injecting the viscoelastic substance under the membranes and simplified its removal at the end of surgery.

Computer-assisted spectral electroretinography in vitrectomy patients.

Computer-assisted spectral electroretinography (CASE), using full field stimulation in the presence of a rod saturating background light, has been found to be a useful means of evaluating retinal function in patients with vitreal opacities. By this means, cone electroretinograms (ERGs) to white as well as spectrally selective stimuli could easily be detected in 22 of 24 eyes with vitreal opacities obscuring any view of the fundus and with minimal or no detectable ERGs to standard single flash stimuli. The responses to spectral stimuli in the presence of a rod saturating background light provides a means of estimating the optical density of the opacity. The results indicate that most patients undergoing vitrectomy for such opacities have considerable superimposed retinal damage and that the opacities themselves are seldom sufficiently dense to decrease the ERG to any great extent. Five eyes studied before and after vitrectomy indicate that successful vitrectomy has no effect on the ERG. The results suggest that CASE may be a useful substitute to the bright flash ERG for evaluating global retinal function behind an opaque media.