Methods For Intraocular Delivery In Small And Large Animal Models

TOPICAL COLLECTIONS

Guest Editors

Hemant Khanna

UMass Medical School

Dr. Hemant Khanna obtained his PhD degree from The University of Delhi India and postdoctoral training in the Kellogg Eye Center at University of Michigan. Dr. Khanna is currently a tenured Associate Professor at the University of Massachusetts Medical School. His laboratory focuses on delineating the molecular mechanisms involved in photoreceptor degeneration during disease and utilizing such knowledge to develop novel therapeutic paradigms for blinding disorders. Dr. Khanna has a background in genetics, biochemistry, molecular biology, and cell biology of retinal degenerative diseases. He utilizes a variety of experimental approaches, including genetic, cell biological, and biochemical approaches to understand the mechanisms of photoreceptor degeneration. His laboratory routinely performs in vivo ocular delivery of AAV vectors and small molecules into mice and large animals (such as pigs and monkeys). The Khanna lab was the first to demonstrate the potential of minigenes to delay retinal degeneration in mice. Dr. Khanna is also a member of the Horae Gene Therapy Center and Li Weibo Rare Disease Institute at the University of Massachusetts Medical School (https://www.umassmed.edu/khannalab/).

Laura Moreno-Leon

UMass Medical School

Dr. Moreno-Leon is a research instructor in the department of Ophthalmology and Visual Sciences at University of Massachusetts (UMASS) Medical School. After obtaining her PhD degree from University of Nice Côte d’Azur in France, she completed her Post-Doctoral training in Dr. Hemant Khanna’s team at UMASS Medical school. Dr. Moreno-Leon acquired a cellular biology and molecular biology background during her PhD training while she studied the role of long non-coding RNAs involved in lung adenocarcinoma development and progression. She also performed gene editing approach to measure the therapeutic potential of targeting non-coding RNA in cancer therapies. With a strong interest in gene therapy, her post-doctoral training focused on bridging the gap between bench and bedside in the field of retinal degeneration by studying the function of micro-RNAs and RNA splicing during retinal development and disease. She has also proposed an alternative treatment strategy for a severe form of retinitis pigmentosa (RP), X-linked RP due to mutations in the RPGR gene.

Collection Overview

The complexity of eyes has perplexed many scientists, such as the likes of Charles Darwin. The retina, a thin light-sensitive tissue in the back of the eye, is the first responder to light. Inherited retinal degenerative diseases are a major cause of blindness. Gene therapy is a promising technology for treating genetic eye diseases. With the FDA approval of the first gene therapy drug for an inherited form of retinal degeneration, there has been renewed interest in the field. A challenge to gene delivery in the retina is the route of delivery. The retina can be accessed via three distinct routes: the intravitreal, the subretinal and the suprachoroidal. The choice of the route depends upon the targeted cell type. While intravitreal injections are relatively safer and can be performed in the doctor’s office, the subretinal injection is an invasive surgical procedure in which therapeutics are delivered between the photoreceptors and the RPE. This vitro-retinal technique requires an operating room, is usually performed under general anesthesia, and carries the risk of retinal tears, detachments, and macular holes. Suprachoroidal delivery is a relatively new breakthrough in the retinal gene delivery landscape. Given the significance of the delivery route to the target cell-type in the retina, it is imperative to understand the complexities associated with each route in a rodent model. The aim of the current collection is to demonstrate standardized protocols of procedures used to deliver therapeutic material to the different parts of the eye, and provide new information on already existing protocols, which will be useful to researchers working on rodents and larger animal models.