Interrogating the intersection between diet and ocular autoimmunity
探究饮食与眼部自身免疫之间的交叉点
基本信息
- 批准号:10419170
- 负责人:
- 金额:$ 58.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:AdjuvantAdoptive TransferAdverse effectsAnatomyAnti-Inflammatory AgentsAutoimmuneAutoimmune DiseasesAutoimmunityBiological AssayBlindnessBloodBrainCardiovascular systemCellsCentral Nervous System DiseasesClinical TrialsConsumptionDemyelinationsDiagnosticDietDiet HabitsDiseaseEnvironmentErythrocytesErythropoietinExperimental Autoimmune EncephalomyelitisEyeFatty AcidsFatty acid glycerol estersFlareFoodFumaratesGoalsHealthHomeostasisITGAM geneImmuneImmune ToleranceImmunohistochemistryImmunologicsIncidenceInflammationInflammatoryInterleukin-17Intestinal permeabilityIntestinesLeaky GutLife StyleLinkMeasurementMediatingMedium chain triglyceridesMetabolicMetabolic syndromeModelingMultiple SclerosisMultiple Sclerosis LesionsMusNatural ImmunityNeuromyelitis OpticaOcular PathologyOptic NerveOptic NeuritisOpticsOralOutcomePainPathogenicityPathologyPatientsPlasmaPopulationPredispositionProcessPsychophysicsRecombinantsReducing dietReporterResolutionRetinaSiteSjogren&aposs SyndromeSourceSpinal CordT-LymphocyteTestingTimeTreatment EfficacyUveitisVisionWorkadaptive immunityautoreactive T cellbasecytokinedesigndiagnostic biomarkerdietarydysbiosisempoweredexperiencegut healthgut homeostasisgut microbiomeimmunoregulationimprovedin vivoinflammatory markerinflammatory milieuketogenic dietlipidomicsmigrationmonocytemotor deficitmouse modelmultiple sclerosis patientmultiple sclerosis treatmentnerve damageneuroprotectionnovelnutritional approachoculomotorprematurepreservationpreventreconstitutionremyelinationrepairedstandard of caresystemic inflammatory responsetreatment responsevisual motor
项目摘要
5-8% of the US population suffers from at least one autoimmune disease. An upward trajectory has
occurred in the last few decades, implicating diet, lifestyle, environment, and improved diagnostics. The
contributions of diet to this increased incidence have been attributed to the excessive consumption of ultra-
processed foods that drive systemic inflammation. Just as poor dietary habits can compromise health, diseases
can potentially be treated or prevented by diets that promote and restore metabolic homeostasis. Consistent
with this notion, we have demonstrated that a well-formulated ketogenic diet (KD), containing medium chain
triglycerides as the primary source of fat, can mitigate the visual and motor deficits in a mouse model of
autoimmunity called MOG-EAE. This model reconstitutes many of the signature ocular and motor pathologies
experienced by patients with Multiple Sclerosis (MS) and Neuromyelitis Optica. The goals of this application
are: (1) to identify the immuno-modulatory mechanisms by which a well-formulated KD preserves metabolic
homeostasis, gut health, and immune tolerance, (2) to determine if a KD can serve as an adjuvant to enhance
the vision-sparing capacity of existing MS treatments and (3) to determine if the KD can repair damaged nerves
by promoting remyelination. Our leading hypothesis is that a well-formulated KD promotes immune tolerance
and neuroprotection by creating a systemic anti-inflammatory milieu. Specific Aim 1 will identify the mechanisms
linking gut integrity and plasma fatty acids to optic neuritis, a painful and often blinding inflammation of the optic
nerve experienced by MS patients. Specific Aim 2 will determine if the KD can enhance the vision-sparing
capacity of several current MS treatments. Specific Aim 3 will identify novel immunological mechanisms that
mediate the efficacy of the KD during autoimmune challenge. This work combines psychophysical
measurements of vision, a novel reporter mouse, gut permeability assays, high resolution lipidomics, adoptive
transfer assays, and blood analyses for markers of inflammation and metabolic/cardiovascular status. This work
is distinguished from previous studies by comparing the anatomic-specific effects of the KD at each of the primary
sites of MS lesions (optic nerve, spinal cord, and brain).
These studies are designed to overcome the serious adverse effects associated with current MS
treatments by empowering patients with a readily-implementable dietary strategy to prevent or reduce flare ups
of optic neuritis and other debilitating sequelae. Additionally, these findings will provide a framework to facilitate
interpreting outcomes from the numerous clinical trials currently testing the KD across a range of diseases.
5%-8%的美国人口至少患有一种自身免疫性疾病。一个向上的轨迹已经
发生在过去几十年,与饮食、生活方式、环境和改进的诊断有关。这个
饮食对发病率增加的贡献被归因于过度摄入超
会引发全身炎症的加工食品。正如不良的饮食习惯会损害健康、疾病一样
可以通过促进和恢复代谢动态平衡的饮食来治疗或预防。一致
在这个概念下,我们已经证明了含有中链的配方良好的生酮饮食(KD)
甘油三酯作为脂肪的主要来源,可以缓解小鼠的视觉和运动障碍
自身免疫性疾病称为MOG-EAE。这个模型重建了许多标志性的眼部和运动病理。
多发性硬化症(MS)和视神经脊髓炎患者经历的。此应用程序的目标是
是:(1)确定免疫调节机制,通过这些机制,良好配方的KD保存代谢
动态平衡、肠道健康和免疫耐受,(2)确定KD是否可以作为佐剂来增强
现有多发性硬化症治疗的视觉保护能力;(3)确定KD是否可以修复受损的神经
通过促进髓鞘再生。我们的主要假设是,配方良好的KD可促进免疫耐受
以及通过创造全身性抗炎环境来保护神经。具体目标1将确定这些机制
肠道完整性和血浆脂肪酸与视神经炎有关,视神经炎是一种疼痛且经常致盲的视神经炎症
多发性硬化症患者的神经体验。具体目标2将决定KD是否能增强视力保护
目前几种多发性硬化症治疗的能力。具体目标3将确定新的免疫机制,
在自身免疫攻击过程中调节KD的疗效。这项工作结合了心理物理学
视力测量,新型报告小鼠,肠道通透性分析,高分辨率脂质组学,采用
转移分析,以及血液分析炎症和代谢/心血管状态的标志物。这部作品
与以前的研究不同的是,通过比较KD在每个初级
多发性硬化病变的部位(视神经、脊髓和脑)。
这些研究旨在克服与当前多发性硬化症相关的严重不良影响
通过为患者提供易于实施的饮食策略来预防或减少突发事件的治疗
视神经炎和其他令人衰弱的后遗症。此外,这些发现将提供一个框架,以促进
解释目前在一系列疾病中测试KD的众多临床试验的结果。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Scott M Plafker其他文献
Scott M Plafker的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Scott M Plafker', 18)}}的其他基金
Interrogating the intersection between diet and ocular autoimmunity
探究饮食与眼部自身免疫之间的交叉点
- 批准号:
10597231 - 财政年份:2022
- 资助金额:
$ 58.08万 - 项目类别:
Treatment strategies for autoimmune demyelinating optic neuritis
自身免疫性脱髓鞘性视神经炎的治疗策略
- 批准号:
9249047 - 财政年份:2016
- 资助金额:
$ 58.08万 - 项目类别:
OKHSC COBRE: THE ROLE OF THE UBIQUITIN SYSTEM IN RETINAL DEGENERATION
OKHSC COBRE:泛素系统在视网膜变性中的作用
- 批准号:
8360280 - 财政年份:2011
- 资助金额:
$ 58.08万 - 项目类别:
Control of redox regulators by the ubiquitin system
泛素系统对氧化还原调节剂的控制
- 批准号:
8727042 - 财政年份:2011
- 资助金额:
$ 58.08万 - 项目类别:
Control of redox regulators by the ubiquitin system
泛素系统对氧化还原调节剂的控制
- 批准号:
8536839 - 财政年份:2011
- 资助金额:
$ 58.08万 - 项目类别:
Control of redox regulators by the ubiquitin system
泛素系统对氧化还原调节剂的控制
- 批准号:
8106682 - 财政年份:2011
- 资助金额:
$ 58.08万 - 项目类别:
Control of redox regulators by the ubiquitin system
泛素系统对氧化还原调节剂的控制
- 批准号:
8320952 - 财政年份:2011
- 资助金额:
$ 58.08万 - 项目类别:
OKHSC COBRE: PROTECTING THE RETINA FROM OXIDATIVE STRESS
OKHSC COBRE:保护视网膜免受氧化应激
- 批准号:
8167973 - 财政年份:2010
- 资助金额:
$ 58.08万 - 项目类别:
OKHSC COBRE: UBIQUITIN IN HYPERGLYCEMIA-INDUCED MESANGIAL CELL HYPERTROPHY
OKHSC COBRE:泛素在高血糖引起的系膜细胞肥大中的作用
- 批准号:
7959775 - 财政年份:2009
- 资助金额:
$ 58.08万 - 项目类别:
OKHSC COBRE: UBIQUITIN IN HYPERGLYCEMIA-INDUCED MESANGIAL CELL HYPERTROPHY
OKHSC COBRE:泛素在高血糖引起的系膜细胞肥大中的作用
- 批准号:
7721020 - 财政年份:2008
- 资助金额:
$ 58.08万 - 项目类别:
相似海外基金
Time to ATTAC: Adoptive Transfer of T cells Against gp100+ Cells to treat LAM
ATTAC 时间:针对 gp100 细胞的 T 细胞过继转移来治疗 LAM
- 批准号:
10682121 - 财政年份:2023
- 资助金额:
$ 58.08万 - 项目类别:
Phase I clinical trial of adoptive transfer of autologous folate receptor-alpha redirected CAR T cells for ovarian cancer
自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
- 批准号:
10576370 - 财政年份:2022
- 资助金额:
$ 58.08万 - 项目类别:
Phase I clinical trial of adoptive transfer of autologous folate receptor-alpha redirected CAR T cells for ovarian cancer
自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
- 批准号:
10387023 - 财政年份:2022
- 资助金额:
$ 58.08万 - 项目类别:
Determining mechanisms of enhanced antitumor efficacy of four-day expanded Th17 cells for adoptive transfer
确定用于过继转移的四天扩增 Th17 细胞增强抗肿瘤功效的机制
- 批准号:
10248409 - 财政年份:2019
- 资助金额:
$ 58.08万 - 项目类别:
A phase I clinical study of adoptive transfer of regulatory T cells (Tregs) and low-dose interleukin-2 (IL-2) for the treatment of chronic graft-versus-host disease (GVHD): gene-marking to inform rational combination therapy
调节性 T 细胞 (Treg) 和低剂量白细胞介素 2 (IL-2) 过继转移治疗慢性移植物抗宿主病 (GVHD) 的 I 期临床研究:基因标记为合理的联合治疗提供信息
- 批准号:
nhmrc : GNT1163111 - 财政年份:2019
- 资助金额:
$ 58.08万 - 项目类别:
Project Grants
Determining mechanisms of enhanced antitumor efficacy of four-day expanded Th17 cells for adoptive transfer
确定用于过继转移的四天扩增 Th17 细胞增强抗肿瘤功效的机制
- 批准号:
10462684 - 财政年份:2019
- 资助金额:
$ 58.08万 - 项目类别:
Gene edited lymphoid progenitors for adoptive transfer as a treatment of primary immunodeficiency
基因编辑的淋巴祖细胞用于过继转移作为原发性免疫缺陷的治疗
- 批准号:
398018062 - 财政年份:2018
- 资助金额:
$ 58.08万 - 项目类别:
Research Grants
Overcoming immune suppression in cancer by targeting PSGL-1 in T cells used for adoptive transfer
通过靶向用于过继转移的 T 细胞中的 PSGL-1 克服癌症中的免疫抑制
- 批准号:
9308643 - 财政年份:2017
- 资助金额:
$ 58.08万 - 项目类别:
Overcoming immune suppression in cancer by targeting PSGL-1 in T cells used for adoptive transfer
通过靶向用于过继转移的 T 细胞中的 PSGL-1 克服癌症中的免疫抑制
- 批准号:
9447149 - 财政年份:2017
- 资助金额:
$ 58.08万 - 项目类别:
Targeting Cancer miRNAs by Adoptive Transfer of Programmed B Lymphocytes
通过程序化 B 淋巴细胞的过继转移靶向癌症 miRNA
- 批准号:
8893915 - 财政年份:2014
- 资助金额:
$ 58.08万 - 项目类别:














{{item.name}}会员




