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.

申请摘要 这是Bryce Chiang，MD博士的K08指导的临床科学家研究职业发展奖。 眼科居住地完成后，Chiang博士将被聘为眼科助理教授 斯坦福大学的拜尔斯眼科研究所。本申请的目的是为Chiang博士提供所需的培训，Mentalship， 并支持成为具有眼药输送专业知识的研究者，特别是针对视神经头的研究者。临床 青光眼研究金将在25％的临床时间内完成，这是通过K08奖的时间表完成。 Chiang博士有 组装了一个由视神经神经保护和神经 - 再生;和眼药输送专家Mark Prausntiz博士。此外，他还确定了主要合作者 包括眼药输送专家Uday Kompella博士；视神经疾病和动物的专家乔伊斯·洛（Joyce Liao）博士 模型；眼病理学家乔纳森·林博士；玻璃体视网膜外科医生Vinit Mahajan博士。 光学神经病是影响视神经的一系列毁灭性视力威胁性疾病。没有方法可以 有选择地将理论传递到视神经头，而有针对性的分娩可以改善由于生理的结果 时空提示和/或选择性靶向受伤的组织。提出的技术是通过 螺旋体到孔洞（SCONE）注射。中心假设是Scone注入技术可以 用于选择性地靶向视神经头，用这种方法提供的疗法将更有效 与玻璃体内或肌内视神经注射相比。 AIM 1的假设是Scone注射可以是 进一步优化，该技术不会在功能或结构上影响视神经头组织。假设 AIM 2是Scone注射将比玻璃体内或肌内视神经更局限于视神经头部。 注射。 AIM 3的假设是传递到视神经头的睫状神经营养因子（CNTF） 游离蛋白，或在持续释放聚合物中，或用AAV转导的局部细胞会带来更大的神经保护作用，并且 视神经损伤后的玻璃体内或乳房内注射的再生。这项研究可能会改善交付 视神经头的技术将在K奖授予结束之前构成R01申请的基础。