Inverse correlation between fatty acid transport protein 4 and vision in Leber congenital amaurosis associated with RPE65 mutation

Li, Songhua; Gordon, William C.; Bazán, Nicolás G.; Jin, Minghao

doi:10.1073/pnas.2012623117

Cited by 5 publications

(1 citation statement)

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“…1 G). In mouse models of Leber congenital amaurosis caused by shortage of 11- cis -retinal supply, opsins are misfolded, 42 – 44 which might induce upregulation of RIPK1 in the chromophore-deficient retina.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin Inhibits Light-Induced Necrosome Activation Occurring in Wild-Type, but not RPE65-Null, Mouse Retina

Jin

2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Both photodamage and aberrant visual cycle contribute to disease progress of many retinal degenerative disorders, whereas the signaling pathways causing photoreceptor death remain unclear. Here we investigated the effects of intense photo-stress on (1) necrosome activation in wild-type and RPE65-null mice, (2) interaction of p62/Sequestosome-1 with the necrosome proteins, and (3) the effects of rapamycin on photodamage-induced necrosome activation and retinal degeneration in wild-type mice. Methods Dark-adapted rd 12 mice and 129S2/Sv mice with or without rapamycin treatment were exposed to 15,000 lux light for different times. Expression levels and subcellular localization of proteins were determined through immunoblot and immunohistochemical analyses. Cone sheaths were stained with peanut agglutinin. Correlation between photoreceptor degeneration and receptor-interacting protein kinase-1 (RIPK1) expression was assessed with Spearman's correlation analysis. Protein-protein interaction was analyzed by immunoprecipitation. Results Intense light caused rod and cone degeneration accompanied by a significant increase in RIPK1-RIPK3 expressions, mixed lineage kinase domain-like protein phosphorylation, damage-associated molecular patterns protein release, and inflammatory responses in wild-type mouse retina. The same intense light did not induce the necrosome activation in rd 12 retina, but it did in rd 12 mice that received 9- cis -retinal supply. RIPK1 expression levels are positively correlated with the degrees of rod and cone degeneration. Photodamage upregulated expression and interaction of the p62 autophagosome cargo protein with the necrosome proteins, whereas rapamycin treatment attenuated the light-induced necrosome activation and photoreceptor degeneration. Conclusions Necrosome activation contributed to photodamage-induced rod and cone degeneration. The visual cycle and autophagy are the important therapeutic targets to alleviate light-induced retinal necroptosis.

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Section: Discussionmentioning

confidence: 99%

Rapamycin Inhibits Light-Induced Necrosome Activation Occurring in Wild-Type, but not RPE65-Null, Mouse Retina

Jin

2022

Invest. Ophthalmol. Vis. Sci.

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Tasks activating the default mode network map multiple functional systems

Mancuso

Liloia

et al. 2022

Brain Struct Funct

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Recent developments in network neuroscience suggest reconsidering what we thought we knew about the default mode network (DMN). Although this network has always been seen as unitary and associated with the resting state, a new deconstructive line of research is pointing out that the DMN could be divided into multiple subsystems supporting different functions. By now, it is well known that the DMN is not only deactivated by tasks, but also involved in affective, mnestic, and social paradigms, among others. Nonetheless, it is starting to become clear that the array of activities in which it is involved, might also be extended to more extrinsic functions. The present meta-analytic study is meant to push this boundary a bit further. The BrainMap database was searched for all experimental paradigms activating the DMN, and their activation likelihood estimation maps were then computed. An additional map of task-induced deactivations was also created. A multidimensional scaling indicated that such maps could be arranged along an anatomo-psychological gradient, which goes from midline core activations, associated with the most internal functions, to that of lateral cortices, involved in more external tasks. Further multivariate investigations suggested that such extrinsic mode is especially related to reward, semantic, and emotional functions. However, an important finding was that the various activation maps were often different from the canonical representation of the resting-state DMN, sometimes overlapping with it only in some peripheral nodes, and including external regions such as the insula. Altogether, our findings suggest that the intrinsic–extrinsic opposition may be better understood in the form of a continuous scale, rather than a dichotomy.

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Retinal pigment epithelium 65 kDa protein (RPE65): An update

Kiser

2022

Progress in Retinal and Eye Research

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Inverse correlation between fatty acid transport protein 4 and vision in Leber congenital amaurosis associated with RPE65 mutation

Cited by 5 publications

References 68 publications

Rapamycin Inhibits Light-Induced Necrosome Activation Occurring in Wild-Type, but not RPE65-Null, Mouse Retina

Rapamycin Inhibits Light-Induced Necrosome Activation Occurring in Wild-Type, but not RPE65-Null, Mouse Retina

Tasks activating the default mode network map multiple functional systems

Retinal pigment epithelium 65 kDa protein (RPE65): An update

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