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.

应用程序摘要 这是K08指导临床医生科学家研究职业发展奖的申请，为Bryce Chiang，医学博士。 完成眼科实习后，江医生将受聘为该校眼科助理教授。 斯坦福大学拜尔斯眼科研究所。此应用程序的目的是为江博士提供所需的培训、指导、 并支持成为一名在眼科药物输送方面拥有专业知识的调查员，特别是视神经头。一家诊所 青光眼奖学金将在25%的临床时间内完成，直到K08奖的时间表。蒋介石博士 组建了一个由杰弗里·戈德堡博士组成的导师团队，他是视神经保护和神经保护方面的专家 再生；以及眼科药物输送专家Mark Prausntiz博士。此外，他还确定了关键的合作者 包括眼科药物输送专家Uday Kompella博士；视神经疾病和动物专家Joyce Liao博士 模特；乔纳森·林博士，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。没有任何方法可以 选择性地将治疗药物输送到视神经头，由于生理原因，靶向输送可以改善结果 时空提示和/或对受损组织的选择性靶向。建议的技术是通过以下方式进入视神经头 脉络膜上视神经(SCONE)注射。中心假设是斯康注射技术可以 被用来选择性地靶向视神经头，用这种方法提供的治疗将更有效 与玻璃体内或眼眶内视神经注射相比。目标1的假设是司康宁注射可以是 进一步优化，该技术不会从功能或结构上影响视神经头组织。假说 目标二是司康注射将更多地定位于视神经头，而不是玻璃体内或眶内视神经。 打针。目标3的假设是睫状神经营养因子(CNTF)传递到视神经头-或者作为 游离蛋白质，或在缓释聚合物中，或用AAV转导局部细胞-将带来更大的神经保护和 视神经损伤后玻璃体内或眶内注射的再生效果更好。这项研究可能会改善交付情况 技术应用到视神经头，并将在K奖结束前形成R01申请的基础。