The Role of Caspase-12 in Retinal Bystander Cell Death and Innate Immune Responses against MCMV Retinitis.

(1) Background: caspase-12 is activated during cytomegalovirus retinitis, although its role is presently unclear. (2) Methods: caspase-12-/- (KO) or caspase-12+/+ (WT) mice were immunosup eyes were analyzed by plaque assay, TUNEL assay, immunohistochemical staining, western blotting, and real-time PCR. (3) Results: increased retinitis and a more extensive virus spread were detected in the retina of infected eyes of KO mice compared to WT mice at day 14 p.i. Compared to MCMV injected WT eyes, mRNA levels of interferons α, ß and γ were significantly reduced in the neural retina of MCMV-infected KO eyes at day 14 p.i. Although similar numbers of MCMV infected cells, similar virus titers and similar numbers of TUNEL-staining cells were detected in injected eyes of both KO and WT mice at days 7 and 10 p.i., significantly lower amounts of cleaved caspase-3 and p53 protein were detected in infected eyes of KO mice at both time points. (4) Conclusions: caspase-12 contributes to caspase-3-dependent and independent retinal bystander cell death during MCMV retinitis and may also play an important role in innate immunity against virus infection of the retina.

Ontogenesis of the pinealo-retinal neuronal connection in albino rats.

It was accepted for a long time that in mammals there is only retinofugal neuronal connection between the eye and the pineal body (PB). In our previous paper we described that nerve cells were present in hamster PB and these neurons could establish a reverse connection with the retina through a transsynaptic pathway. In adult albino rats neuronal perikarya were not found. In this present experiment it was examined whether the lack of these nerve cells in the PB of adult rats is the result of an apoptotic phenomenon or the lack of migration during the fetal period. Green fluorescence protein expressing pseudorabies virus, spreading only in retrograde direction, was injected into the vitreous body of rats at various postnatal ages. Virus labeled cell bodies were not observed in the PB of adult rats; however, labeling with gradually decreasing number of cells was present in animals aged 3-6, 13-14, 20, 35 and 41 postnatal days. Injection of virus, spreading in anterograde direction (expressing red fluorescence protein), into the PB of young prepubertal animals resulted in labeling in the retina. This observation indicates that the pinealo-retinal connection in prepubertal period is active. Immunostaining revealed that some of the labeled neuronal perikarya showed activated caspase-3 (an apoptotic marker) immunoreactivity. Our results clearly show that the neurons migrate to the PB and later, during the prepubertal period, they disappear. Caspase-3 immnoreactivity indicates that these cells die off by apoptosis.

The Neurobiology of Zika Virus.

Zika virus (ZIVK) represents a new threat to global health, with particular relevance to neuroscientists, due to associated newborn and adult neurological disease. Consequences of vertical infection include microcephaly with brain and eye anomalies, and consequences of adult infection include Guillain-Barré syndrome (GBS) and meningoencephalitis. Recent data suggest specific vulnerability of neural progenitors to infection, leading to cell death and brain calcification, reminiscent of other viral syndromes. Prevailing models suggest entry into neuronal stem cells through transmembrane receptors, hijacking cellular signaling to interfere with neurogenesis and cell survival. Mechanisms of adult neurological disease are unknown, but recent evidence suggests propensity for infection of adult neural stem cells. Efforts focused on mechanisms of pathogenesis, vulnerabilities, and treatments are urgently needed.