Methods and Models to Investigate Gene Therapy-Associated Uveitis

TOPICAL COLLECTIONS

Guest Editors

Alison Clare

University of Bristol

Dr. Alison Clare is a senior research associate in the Ocular Inflammation Group at the University of Bristol. Her research focuses on the cellular and immune mechanisms underlying ocular degeneration, with the aim of developing translational therapies for eye disease. She has extensive expertise in viral vector-mediated gene delivery to the brain and eye, alongside advanced techniques including tissue imaging, flow cytometry, and transcriptomics. Her recent work has advanced the understanding of immune responses to adeno-associated viral (AAV) vectors in retinal gene therapy, termed gene therapy-associated uveitis (GTAU). In particular, her research has demonstrated how biological factors, including sex and age, can influence responses to AAV-mediated therapies. She is also a strong advocate for greater inclusion in biomedical research to help ensure translational therapies are safe and effective for all populations.

David Copland

University of Bristol

Dr. David Copland is a principal investigator within the Ocular Inflammation Group, based at the University of Bristol. His work has focused on understanding the immune mechanisms that drive inflammation and tissue damage in autoimmune, infectious, neovascular, and degenerative eye disease. This research integrates preclinical models of disease with advanced imaging, immune phenotyping, flow cytometry, and transcriptomic approaches to understand cellular and molecular pathway mechanisms that contribute to acute and persistent chronic inflammation within ocular tissues. Current collaborative research projects are focused on overcoming immune responses to retinal gene therapy vectors (GTAU), the development of translational gene therapy strategies for uveitis, and characterizing the involvement of tissue-resident T cell populations with ocular inflammation linked to systemic inflammatory disease.

Collection Overview

Gene therapy has emerged as a transformative approach for the treatment of inherited and acquired retinal diseases, offering the potential for durable therapeutic benefit after a single intervention. However, intraocular inflammation (IOI), also known as gene therapy-associated uveitis (GTAU), has become an increasingly recognised complication that can affect treatment safety, durability, and visual outcomes. As ocular gene therapy trials expand in scope, there is an urgent need for standardised and robust approaches to study mechanisms, identify risk, and find viable solutions to manage GTAU.

In this Topical Collection, we aim to bring together methodological advances that will improve our ability to define, monitor, and manage inflammatory responses in the eye across all routes of administration, including intravitreal, subretinal, and suprachoroidal delivery. The collection will spotlight emerging and established tools for characterising and treating GTAU, with a focus on the following:

Models of GTAU, including translational models to predict inflammatory risk
Methods to define the cellular and molecular mechanisms of ocular inflammation in GTAU
Biomarkers and assays to measure immunomodulatory effects

By promoting methodological rigor, reproducibility, and cross-disciplinary collaboration, this collection aims to establish a strong research base for understanding and managing GTAU.