We have first observed the nucleation and growth process of carbon nanotubes (CNTs) from iron carbide (Fe 3C) nanoparticles in chemical vapor deposition with C 2H 2 by in situ environmental transmission electron microscopy. Graphitic networks are formed on the fluctuating iron carbide nanoparticles, and subsequently CNTs are expelled from them. Our atomic scale observations suggest that carbon atoms diffuse through the bulk of iron carbide nanoparticles during the growth of CNTs.

Background:The host inflammatory response can contribute to the pathogenesis of retinal degeneration. Results: Photoreceptor proteins in degenerating retinas can activate microglial cells through Toll-like receptor 4 (Tlr4). Conclusion: Microglial activation can be a common pathology of retinal degeneration. Significance: Modulating microglial activation is a potential treatment strategy for human retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa.

Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore, 11-cis-retinal, and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the photoisomered product, all-trans-retinal, can cause severe retinal pathology. Here we lowered peak concentrations of free all-trans-retinal with primary amine-containing FDA-approved drugs that did not inhibit chromophore regeneration in mouse models of retinal degeneration. Schiff base adducts between all-trans-retinal and these amines were identified by mass spectrometry. Adducts were observed in mouse eyes only when an experimental drug protected the retina from degeneration in both short-term and long-term treatment experiments. This study demonstrates a molecular basis of all-trans-retinal-induced retinal pathology and identifies an assemblage of FDA-approved compounds with protective effects against this pathology in a mouse model that displays features of Stargardt’s and age-related retinal degeneration.

Background: Autophagy is a conserved process of lysosome-mediated intracellular degradation. Results: Dysregulation of autophagy is associated with retinal cell death by all-trans-retinal and by light exposure. Conclusion: Autophagy protects the retina from light-induced retinal degeneration. Significance: Dynamic autophagy regulation may influence retinal cell survival under stress and disease conditions.

Many degenerative retinal diseases illustrate retinal inflammatory changes that include infiltration of microglia and macrophages into the subretinal space. In the current study, we examined the role of chemokines in the Abca4-/-Rdh8-/- mouse model of Stargardt disease and the Mertk-/- mouse model of retinitis pigmentosa. PCR array analysis of 84 chemokines and related molecules revealed 84.6-fold elevated expression of Ccl3 (MIP-1a) 24 h after light exposure in Abca4-/-Rdh8-/- mice. Only MIP-1 chemokines, including Ccl3 and Ccl4, displayed peak expression 24 h after light exposure, and peaked earlier than the other chemokines. Secretion of Ccl3 was documented only in microglia whereas both microglia and RPE cells produced Ccl2. Exposure of Cx3Cr1gfp/ΔAbca4-/-Rdh8-/- mice to intense light resulted in the appearance of Cx3Cr1GFP+ monocytes in the subretinal space. To address the in vivo role of CCL3 in retinal degeneration, Ccl3-/-Abca4-/-Rdh8-/- mice and Ccl3-/-Mertk-/- mice were generated. Following intense light exposure, Ccl3-/-Abca4-/-Rdh8-/- mice displayed persistent retinal inflammation with appearance of Iba-1-positive cells in the subretinal space, severe photoreceptor cell death and increased Ccl4 expression compared with Abca4-/-Rdh8-/- mice. In contrast, Ccl3-/-Abca4-/-Rdh8-/- mice exhibited a milder retinal inflammation and degeneration than Abca4-/-Rdh8-/- mice in age-related chronic retinal degeneration under room light conditions. The deficiency of Ccl3 also attenuated the severity of retinal degeneration in Mertk-/- mice. Taken together, our results indicate that Ccl3 has an essential role in regulating the severity of retinal inflammation and degeneration in these mouse models.

Photoreceptor cell death is the proximal cause of blindness in many retinal degenerative disorders; hence, understanding the gene regulatory networks that promote photoreceptor survival is at the forefront of efforts to combat blindness. Down-regulation of the microRNA (miRNA)-processing enzyme DICER1 in the retinal pigmented epithelium has been implicated in geographic atrophy, an advanced form of age-related macular degeneration (AMD). However, little is known about the function of DICER1 in mature rod photoreceptor cells, another retinal cell type that is severely affected in AMD. Using a conditional-knockout (cKO) mouse model, we report that loss of DICER1 in mature postmitotic rods leads to robust retinal degeneration accompanied by loss of visual function. At 14 wk of age, cKO mice exhibit a 90% reduction in photoreceptor nuclei and a 97% reduction in visual chromophore compared with those in control littermates. Before degeneration, cKO mice do not exhibit significant defects in either phototransduction or the visual cycle, suggesting that miRNAs play a primary role in rod photoreceptor survival. Using comparative small RNA sequencing analysis, we identified rod photoreceptor miRNAs of the miR-22, miR-26, miR-30, miR-92, miR-124, and let-7 families as potential factors involved in regulating the survival of rods.

Chronic inflammation is an important component that contributes to many age-related neurodegenerative diseases, including macular degeneration. Here, we report a role for tolllike receptor 3 (TLR3) in cone-rod dystrophy (

We have elucidated the synergetic role played by molybdenum in iron-catalyzed chemical vapor deposition growth of carbon nanotubes (CNTs) by in situ environmental transmission electron microscopy. Molybdenum can be well accommodated by Fe-based carbide nanoparticle catalysts of M(23)C(6)-type structure (M = Fe and Mo). We have also shown that molybdenum suppresses the nucleation of iron compounds that are known to exhibit no catalytic activity for the growth of CNTs.