Localization, safety, and efficacy of optic nerve injections

视神经注射的定位、安全性和有效性

• 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
• 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

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）专业知识的研究者。临床一 青光眼研究金将在 K08 奖项时间表的 25% 临床时间内完成。蒋博士有 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 再生;以及眼部药物输送专家 Mark Prausntiz 博士。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； Joyce Liao博士，视神经疾病和动物专家 模型； Jonathan Lin 博士，眼科病理学家； 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。没有方法可以 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以下方式进入视神经乳头 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 注入可以 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。假设 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 注射。目标 3 的假设是将睫状神经营养因子 (CNTF) 传递至视神经乳头——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。该研究可能会改善交付 视神经乳头技术，并将在 K 奖结束前构成 R01 应用的基础。