Localization, safety, and efficacy of optic nerve injections

视神经注射的定位、安全性和有效性

基本信息

批准号：
10350009
负责人：
Bryce Chiang
金额：
$ 17.26万
依托单位：
STANFORD UNIVERSITY
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：
2022-09-30 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10350009
关键词：
Address Affect American Animal Model Animals Attention Autopsy Award Axon Biology Caliber Catheters Cells Ciliary Neurotrophic Factor Clinical Cues Data Dependovirus Disease Disease model Doctor of Philosophy Dose Drug Delivery Systems Edema Electroretinography Eye FDA approved Fellowship Formulation Functional disorder Fundus photography Glaucoma Growth Factor Health Histology Human Infusion procedures Injections Institutes K-Series Research Career Programs Label Lead Length Measures Mentors Mentorship Metabolic Methods Natural regeneration Needles Nerve Regeneration Neuroglia Operative Surgical Procedures Ophthalmology Optic Disk Optic Nerve Optic Nerve Injuries Optical Coherence Tomography Optics Oryctolagus cuniculus Pathogenesis Pathologist Pathway interactions Patients Pattern Physiological Polymers Prevention Proteins Radial Reporter Research Research Personnel Residencies Retinal Detachment Retinal Ganglion Cells Retinal Perforations Route Safety Scientist Structure of central vein of the retina Surgeon Techniques Technology Therapeutic Time TimeLine Tissues Toxic effect Tracer Training Viscosity Vision Work axon growth axon injury axon regeneration design improved improved outcome in vivo injured macromolecule nanoparticle neuronal cell body neuroprotection neurotransmission non-invasive imaging novel optic nerve disorder optical imaging particle preclinical study professor retinal ganglion cell regeneration retinal nerve fiber layer side effect skills small molecule spatiotemporal targeted delivery therapeutic candidate tonometry tool translational therapeutics

项目摘要

APPLICATION SUMMARY This is a K08 Mentored Clinician Scientist Research Career Development Award application for Bryce Chiang, MD PhD. Upon completion of ophthalmology residency, Dr. Chiang will be hired as an Assistant Professor of Ophthalmology at the Byers Eye Institute at Stanford. The purpose of this application is to provide Dr. Chiang with the needed training, mentorship, and support to become an investigator with expertise in ocular drug delivery, specifically to the optic nerve head. A clinical glaucoma fellowship will be completed during the 25% clinical time through the timeline of the K08 award. Dr. Chiang has assembled a mentorship team consisting of Dr. Jeffrey Goldberg, an expert on optic nerve neuro-protection and neuro- regeneration; and Dr. Mark Prausntiz, an expert in ocular drug delivery. In addition, he has identified key collaborators including Dr. Uday Kompella, an expert in ocular drug delivery; Dr. Joyce Liao, an expert in optic nerve diseases and animal models; Dr. Jonathan Lin, an ocular pathologist; Dr. Vinit Mahajan, a vitreoretinal surgeon. Optic neuropathy is a class of devastating vision threatening diseases that affect the optic nerve. There are no methods to selectively deliver therapeutics to the optic nerve head, and targeted delivery could improve outcomes due to physiologic spatiotemporal cues and/or selective targeting of injured tissue. The proposed technique is to access the optic nerve head by a SupraChoroidal-to-Optic-NErve (SCONE) injection. The central hypothesis is that the SCONE injection technique can be used to selectively target optic nerve head, and that therapies delivered with this method will be more efficacious compared with intravitreal or intraorbital optic nerve injections. The hypothesis of Aim 1 is that SCONE injection can be further optimized, and the technique will not impact the optic nerve head tissue functionally or structurally. The hypothesis of Aim 2 is that SCONE injection will be more localized to optic nerve head than intravitreal or intraorbital optic nerve injections. The hypothesis of Aim 3 is that Ciliary NeuroTrophic Factor (CNTF) delivered to the optic nerve head–either as free protein, or in a sustained release polymer, or transducing local cells with AAV–will bring greater neuroprotection and regeneration than intravitreal or intraorbital injections after optic nerve injury. The research may lead to improved delivery techniques to the optic nerve head, and will form the basis of an R01 application before the end of the K award.

应用摘要这是 Bryce Jiang 医学博士的 K08 指导临床科学家研究职业发展奖申请。完成眼科住院医师实习后，蒋医生将被聘为眼科助理教授斯坦福大学拜尔斯眼科研究所此应用程序的目的是为蒋博士提供所需的培训、指导、并支持成为一名具有眼部药物输送（特别是视神经乳头临床）专业知识的研究者。青光眼研究金将在蒋博士确定的 K08 奖项时间表的 25% 临床时间内完成。组建了由视神经神经保护和神经保护专家 Jeffrey Goldberg 博士组成的导师团队此外，他还确定了关键合作者。其中包括眼部药物输送专家 Uday Kompella 博士、视神经疾病和动物专家 Joyce Liao 博士；模型；Jonathan Lin 博士，眼部病理学家；Vinit Mahajan 博士，玻璃体视网膜外科医生。视神经病变是一类影响视神经的破坏性视力威胁疾病，目前尚无治疗方法。选择性地将治疗药物递送至视神经乳头，并且有针对性的递送可以改善由于生理原因而导致的结果时空线索和/或选择性靶向受伤组织所提出的技术是通过访问视神经乳头。脉络膜上视神经 (SCONE) 注射中心假设是 SCONE 注射技术可以。用于选择性地靶向视神经乳头，并且用这种方法提供的治疗将更加有效与玻璃体内或眼眶内视神经注射相比，目标 1 的假设是 SCONE 注射可以。进一步优化，该技术不会对视神经乳头组织的功能或结构产生影响。目标 2 是 SCONE 注射将比玻璃体内或眼眶内视神经更局限于视神经乳头目标 3 的假设是将睫状神经营养因子 (CNTF) 递送至视神经乳头——或者作为游离蛋白质，或缓释聚合物，或用 AAV 转导局部细胞——将带来更好的神经保护和视神经损伤后的再生效果优于玻璃体内或眼眶内注射，该研究可能会改善分娩效果。视神经乳头技术，并将在 K 奖结束前构成 R01 应用的基础。