新型 NGF 递送系统介导糖尿病角膜病变中的长期神经再生

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Pub Date : 2024-10-24 DOI:10.2337/db24-0393
Lin Cong, Benxiang Qi, Shijiu Chen, Ruiling Liu, Suxia Li, Qingjun Zhou, Yihai Cao, Bi Ning Zhang, Lixin Xie
{"title":"新型 NGF 递送系统介导糖尿病角膜病变中的长期神经再生","authors":"Lin Cong, Benxiang Qi, Shijiu Chen, Ruiling Liu, Suxia Li, Qingjun Zhou, Yihai Cao, Bi Ning Zhang, Lixin Xie","doi":"10.2337/db24-0393","DOIUrl":null,"url":null,"abstract":"Diabetic keratopathy (DK) is a common chronic metabolic disorder that causes ocular surface complications. Among various therapeutic approaches, local delivery of nerve growth factor (NGF) remains the most effective treatment for DK. However, achieving a sustained therapeutic effect with NGF and the frequent drug delivery burden remain challenging during clinical practice. Here, we developed a novel adeno-associated virus (AAV)-based NGF delivery system that achieved one-year-long-lasting effects by a single injection. We refined the corneal stromal injection technique, resulting in reduced corneal edema and improved AAV distribution homogeneity. AAV serotype AAV.rh10 exhibited high tropism and specificity to corneal nerves. A dose of 2×109 vector genomes (vg) was determined to achieve efficient Ngf gene expression without inducing corneal immune responses. Moreover, NGF protein was highly expressed in trigeminal ganglion (TG) through a retrograde transport mechanism, indicating the capacity for repairing corneal nerve damage both at the root and corneal nerve endings. In a mouse DK model, a single injection of AAV-Ngf into the corneal stroma led to marked corneal nerve regeneration for over 5 months. Together, we provide a novel therapeutic paradigm for long-term effective treatment of DK and this therapeutic approach is superior to current DK therapies.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-term nerve regeneration in diabetic keratopathy mediated by a novel NGF delivery system\",\"authors\":\"Lin Cong, Benxiang Qi, Shijiu Chen, Ruiling Liu, Suxia Li, Qingjun Zhou, Yihai Cao, Bi Ning Zhang, Lixin Xie\",\"doi\":\"10.2337/db24-0393\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Diabetic keratopathy (DK) is a common chronic metabolic disorder that causes ocular surface complications. Among various therapeutic approaches, local delivery of nerve growth factor (NGF) remains the most effective treatment for DK. However, achieving a sustained therapeutic effect with NGF and the frequent drug delivery burden remain challenging during clinical practice. Here, we developed a novel adeno-associated virus (AAV)-based NGF delivery system that achieved one-year-long-lasting effects by a single injection. We refined the corneal stromal injection technique, resulting in reduced corneal edema and improved AAV distribution homogeneity. AAV serotype AAV.rh10 exhibited high tropism and specificity to corneal nerves. A dose of 2×109 vector genomes (vg) was determined to achieve efficient Ngf gene expression without inducing corneal immune responses. Moreover, NGF protein was highly expressed in trigeminal ganglion (TG) through a retrograde transport mechanism, indicating the capacity for repairing corneal nerve damage both at the root and corneal nerve endings. In a mouse DK model, a single injection of AAV-Ngf into the corneal stroma led to marked corneal nerve regeneration for over 5 months. Together, we provide a novel therapeutic paradigm for long-term effective treatment of DK and this therapeutic approach is superior to current DK therapies.\",\"PeriodicalId\":11376,\"journal\":{\"name\":\"Diabetes\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2337/db24-0393\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2337/db24-0393","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

糖尿病性角膜病(DK)是一种常见的慢性代谢性疾病,会引起眼表并发症。在各种治疗方法中,局部给药神经生长因子(NGF)仍然是治疗 DK 的最有效方法。然而,在临床实践中,实现 NGF 的持续治疗效果以及频繁给药带来的负担仍是一项挑战。在此,我们开发了一种基于腺相关病毒(AAV)的新型 NGF 给药系统,只需注射一次,就能获得长达一年的持久疗效。我们改进了角膜基质注射技术,从而减轻了角膜水肿,提高了 AAV 分布的均匀性。AAV血清型AAV.rh10表现出对角膜神经的高度滋养性和特异性。2×109载体基因组(vg)的剂量可实现Ngf基因的高效表达,且不会诱发角膜免疫反应。此外,NGF蛋白通过逆行运输机制在三叉神经节(TG)中高表达,表明其有能力修复角膜神经根和角膜神经末梢的损伤。在小鼠 DK 模型中,将 AAV-Ngf 单次注射到角膜基质可使角膜神经再生超过 5 个月。总之,我们为长期有效治疗 DK 提供了一种新的治疗模式,这种治疗方法优于目前的 DK 治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Long-term nerve regeneration in diabetic keratopathy mediated by a novel NGF delivery system
Diabetic keratopathy (DK) is a common chronic metabolic disorder that causes ocular surface complications. Among various therapeutic approaches, local delivery of nerve growth factor (NGF) remains the most effective treatment for DK. However, achieving a sustained therapeutic effect with NGF and the frequent drug delivery burden remain challenging during clinical practice. Here, we developed a novel adeno-associated virus (AAV)-based NGF delivery system that achieved one-year-long-lasting effects by a single injection. We refined the corneal stromal injection technique, resulting in reduced corneal edema and improved AAV distribution homogeneity. AAV serotype AAV.rh10 exhibited high tropism and specificity to corneal nerves. A dose of 2×109 vector genomes (vg) was determined to achieve efficient Ngf gene expression without inducing corneal immune responses. Moreover, NGF protein was highly expressed in trigeminal ganglion (TG) through a retrograde transport mechanism, indicating the capacity for repairing corneal nerve damage both at the root and corneal nerve endings. In a mouse DK model, a single injection of AAV-Ngf into the corneal stroma led to marked corneal nerve regeneration for over 5 months. Together, we provide a novel therapeutic paradigm for long-term effective treatment of DK and this therapeutic approach is superior to current DK therapies.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Diabetes
Diabetes 医学-内分泌学与代谢
CiteScore
12.50
自引率
2.60%
发文量
1968
审稿时长
1 months
期刊介绍: Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.
期刊最新文献
N 6-Methyladenosine demethylase FTO controls macrophage homeostasis in diabetic vasculopathy Emerging concepts and success stories in type 1 diabetes research: a roadmap for a bright future Induction of a Müller glial-specific protective pathway safeguards the retina from diabetes induced damage Long-term nerve regeneration in diabetic keratopathy mediated by a novel NGF delivery system Effect of Hyperketonemia on Myocardial Function in Patients with Heart Failure and Type 2 Diabetes
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1