Oxidative and nitrosative damage are major contributors to cone cell death in retinitis pigmentosa (RP). In this study, we explored the effects of augmenting components of the endogenous antioxidant defense system in models of RP, rd1 and rd10 mice. Unexpectedly, over-expression of superoxide dismutase 1 (SOD1) in rd1 mice increased oxidative damage and accelerated cone cell death. With an elaborate mating scheme, genetically engineered rd10 mice with inducible expression of SOD2, Catalase, or both in photoreceptor mitochondria were generated. Littermates with the same genetic background that did not have increased expression of SOD2 nor Catalase provided ideal controls. Co-expression of SOD2 and Catalase, but not either alone, significantly reduced oxidative damage in the retinas of postnatal day (P) 50 rd10 mice as measured by protein carbonyl content. Cone density was significantly greater in P50 rd10 mice with co-expression of SOD2 and Catalase than rd10 mice that expressed neither, or SOD2 or Catalase alone. Co-expression of SOD2 and Catalase in rd10 mice did not slow rod cell death. These data support the concept of bolstering the endogenous antioxidant defense system as a gene-based treatment strategy for RP, but also indicate that co-expression of multiple components may be needed.
Retinitis pigmentosa (RP) is a collection of diseases in which rod photoreceptors die from a variety of mutations. After rods die, the level of tissue oxygen in the outer retina becomes elevated and there is progressive oxidative damage to cones that ultimately triggers apoptosis. In this study, we investigated the hypothesis that NADPH oxidase (Nox) and/or xanthine oxidase serve as critical intermediaries between increased tissue oxygen and the generation of excessive reactive oxygen species that cause oxidative damage to cones. Apocynin, a blocker of Nox, but not allopurinol, a blocker of xanthine oxidase, markedly reduced the superoxide radicals visualized by hydroethidine in the outer retina in the retinal degeneration‐1 (rd1+/+) model of RP. Compared to rd1+/+ mice treated with vehicle, those treated with apocynin, but not those treated with allopurinol, had significantly less oxidative damage in the retina measured by ELISA for carbonyl adducts. Apocynin‐treated, but not allopurinol‐treated, rd1+/+ mice had preservation of cone cell density, increased mRNA levels for m‐ and s‐cone opsin, and increased mean photopic b‐wave amplitude. In Q344ter mice, a model of dominant RP in which mutant rhodopsin is expressed, apocynin treatment preserved photopic electroretinogram b‐wave amplitude compared to vehicle‐treated controls. These data indicate that Nox, but not xanthine oxidase, plays a critical role in generation of the oxidative stress that leads to cone cell death in RP and inhibition of Nox provides a new treatment strategy.
The quality of the scan image is important in microvascular circulation analysis using optical coherence tomography (OCTA). We aimed to investigate the effect of signal strength (SS) on OCTA metrics and minimum SS level that could be considered optimal. Macular 6 × 6 mm angiography images were acquired, and all subjects were divided into four groups according to the SS (SS 7, SS 8, SS 9, and SS 10) of the OCTA image. Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) metrics of the superficial capillary plexus were compared. In total, 446 eyes from young healthy subjects were included. As the SS increased from 7 to 10, the VD and PD of the total area, and the FAZ area increased significantly (all, p < 0.001), but there were no significant difference between SS 9 and SS 10 in all metrics. Correlation analysis between the SS and each parameter showed a high correlation coefficient (VD, r = 0.668; PD, r = 0.671; FAZ area, r = 0.570; all, p < 0.001). The measurements of VD, PD, and FAZ using OCTA varied significantly with the SS, and at least 9 of SS is recommended. The physician should be careful in the analyses of OCTA measurements showing different values of the SS.
Many recent studies have demonstrated that several known and unknown viruses infect many horticultural plants. However, the elucidation of a viral population and the understanding of the genetic complexity of viral genomes in a single plant are rarely reported. Here, we conducted metatranscriptome analyses using six different peach trees representing six individual peach cultivars. We identified six viruses including five viruses in the family Betaflexiviridae and a novel virus belonging to the family Tymoviridae as well as two viroids. The number of identified viruses and viroids in each transcriptome ranged from one to six. We obtained 18 complete or nearly complete genomes for six viruses and two viroids using transcriptome data. Furthermore, we analyzed single nucleotide variations for individual viral genomes. In addition, we analyzed the amount of viral RNA and copy number for identified viruses and viroids. Some viruses or viroids were commonly present in different cultivars; however, the list of infected viruses and viroids in each cultivar was different. Taken together, our study reveals the viral population in a single peach tree and a comprehensive overview for the diversities of viral communities in different peach cultivars.
BackgroundThe co-infection of diverse viruses in a host plant is common; however, little is known about viral populations and their quasispecies in the host.ResultsHere, we report the first pepper viromes that were co-infected by different types of viral genomes. The pepper viromes are dominated by geminivirus DNA-A followed by a novel carlavirus referred to as Pepper virus A. The two pepper cultivars share similar viral populations and replications. However, the quasispecies for double-stranded RNA virus and two satellite DNAs were heterogeneous and homogenous in susceptible and resistant cultivars, respectively, indicating the quasispecies of an individual virus depends on the host.ConclusionsTaken together, we provide the first evidence that the host plant resistant to viruses has an unrevealed antiviral system, affecting viral quasispecies, not replication.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3838-8) contains supplementary material, which is available to authorized users.
Retinitis pigmentosa (RP) is a major source of blindness caused by a large variety of mutations that lead to the death of rod photoreceptors. After rods die, cones gradually die from progressive oxidative damage. Several types of antioxidant formulations have been shown to reduce cone cell death over a relatively short-time frame, but in order for this strategy to be translated into a new treatment for patients with RP, prolonged effects will be needed. In this study, we determined that orally administered N-acetylcysteine (NAC) reduced cone cell death and preserved cone function by reducing oxidative damage in two models of RP, rd1(+/+) and rd10(+/+) mice. In rd10(+/+) mice, supplementation of drinking water with NAC promoted partial maintenance of cone structure and function for at least 6 months. Topical application of NAC to the cornea also reduced superoxide radicals in the retina and promoted survival and functioning of cones. Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, it is reasonable to consider clinical trials to evaluate the effects of prolonged treatment with NAC in patients with RP.
Viruses are ubiquitous and present in a wide range of settings, from living organisms to various environments. Although viruses are regarded as important pathogens in higher plants, viral populations in specific host plants have not yet been fully examined. This study revealed viral populations in grape berries obtained from a cultivar from a single vineyard using currently available grapevine transcriptomes. Eight viruses and two viroids were identified using 11 grapevine libraries. Virus-associated sequences in each transcriptome ranged from 0.2% (seed) to 8.8% (skin). The amount of viral RNAs and virus copy numbers was quantified, thus revealing the dominant virus or viroid in each individual library. In addition, five viral genomes were successfully assembled de novo using transcriptome data. Phylogenetic analyses revealed that the viruses and viroids might have originated from Europe, along with the host. Single nucleotide variation studies revealed the quasispecies of RNA viruses. Taken together, this study defines complex viral populations in three different grape tissues from a single vineyard.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.