Blue light-induced retinal lesions, intraretinal vascular leakage and edema formation in the all-cone mouse retina.

Little is known about the mechanisms underlying macular degenerations, mainly for the scarcity of adequate experimental models to investigate cone cell death. Recently, we generated R91W;Nrl(-/-) double-mutant mice, which display a well-ordered all-cone retina with normal retinal vasculature and a strong photopic function that generates useful vision. Here we exposed R91W;Nrl(-/-) and wild-type (wt) mice to toxic levels of blue light and analyzed their retinas at different time points post illumination (up to 10 days). While exposure of wt mice resulted in massive pyknosis in a focal region of the outer nuclear layer (ONL), the exposure of R91W;Nrl(-/-) mice led to additional cell death detected within the inner nuclear layer. Microglia/macrophage infiltration at the site of injury was more pronounced in the all-cone retina of R91W;Nrl(-/-) than in wt mice. Similarly, vascular leakage was abundant in the inner and outer retina in R91W;Nrl(-/-) mice, whereas it was mild and restricted to the subretinal space in wt mice. This was accompanied by retinal swelling and the appearance of cystoid spaces in both inner and ONLs of R91W;Nrl(-/-) mice indicating edema in affected areas. In addition, basal expression levels of tight junction protein-1 encoding ZO1 were lower in R91W;Nrl(-/-) than in wt retinas. Collectively, our data suggest that exposure of R91W;Nrl(-/-) mice to blue light not only induces cone cell death but also disrupts the inner blood-retinal barrier. Macular edema in humans is a result of diffuse capillary leakage and microaneurysms in the macular region. Blue light exposure of the R91W;Nrl(-/-) mouse could therefore be used to study molecular events preceding edema formation in a cone-rich environment, and thus potentially help to develop treatment strategies for edema-based complications in macular degenerations.

[HIV-associated Penicillium marneffei infection]. / Die HIV-assoziierte Penicillium-marneffei-Infektion.

We report on an HIV positive patient with a disseminated Penicillium marneffei infection. A 35-year-old Swiss homosexual male with HIV-associated immunodeficiency with a CD4 cell count of 90/mm3 presented with a two-month history of malaise, intermittent fever, loss of weight, unproductive cough and widespread molluscum contagiosum-like skin lesions, mainly on the face. The patient had travelled extensively and had last visited Thailand 19 months before admission. The chest X-ray showed bilateral diffuse reticulonodular markings. The diagnosis was suspected in bronchoalveolar lavage, which showed round-to-oval intracellular yeast cells but also elongated sausage-shaped extracellular forms. The diagnosis was confirmed on culture. Penicillium marneffei was further isolated from the following specimens: blood cultures, bone marrow, stool, skin and tracheal mucosa biopsy. Intravenous amphotericin B therapy led to a complete subsidence of all symptoms and the skin lesions healed without leaving a scar. The infection, with its clinical presentation, epidemiology, diagnostic problems and therapy is reviewed. We stress that since Penicillium marneffei is an increasingly important pathogen in HIV positive patients in Southeast Asia, this fungus can also be imported to Europe by travellers. If immunocompromised patients have molluscum contagiosum-like skin lesions, pneumonitis and a history of travelling in Southeast Asia, disseminated Penicillium marneffei infection should be considered in differential diagnosis.