Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy.
Authors: Crabtree Elizabeth, Uribe Katy, Smith Sara M, Roberts Darby, Salmon Jacklyn H, Bower Jacquelyn J, Song Liujiang, Bastola Prabhakar, Hirsch Matthew L, Gilger Brian C
Journal: PloS one
Summary
Equine recurrent uveitis (ERU) affects up to a quarter of the global equine population and remains a significant cause of vision loss and pain, yet current therapeutic options are poorly targeted and often limited by adverse effects that restrict their clinical use. Researchers used an adeno-associated virus (AAV8) vector to deliver equine interleukin-10 (IL-10) directly into the eye via intravitreal injection, capitalising on this cytokine's natural immune-suppressive properties to test whether a single treatment could prevent or reduce experimentally-induced autoimmune uveitis in a rat model. Both low-dose (2.4×10⁹ vg) and high-dose (2.4×10¹⁰ vg) AAV8-Equine-IL10 treatments significantly reduced clinical inflammatory scores and aqueous humour cell counts compared to controls, with measurable protective effects sustained through 14 days post-induction; histological examination confirmed substantially lower cellular infiltration in treated eyes, and qPCR analysis showed dose-dependent expression of the IL-10 transgene across the ciliary body, retina, cornea, and optic nerve. The single injection was well-tolerated without apparent adverse effects, suggesting AAV-mediated IL-10 gene therapy represents a viable approach to delivering sustained local immunosuppression without the systemic side-effects associated with conventional treatments. For equine practitioners, this work provides preclinical evidence supporting further development of gene therapy as a potential disease-modifying treatment for ERU, though clinical application in horses will require additional safety and efficacy studies before this approach can transition from the laboratory to clinical practice.
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Practical Takeaways
- •AAV-mediated IL10 gene therapy shows promise as a single-injection treatment for equine recurrent uveitis, potentially addressing the side-effect limitations of current long-term anti-inflammatory protocols
- •The therapeutic window appears broad—efficacy was achieved at the lowest tested dose, suggesting potential for dose optimization and reduced treatment burden in clinical practice
- •This represents early-stage preclinical work in rats; further equine-specific studies will be needed before clinical application, but the use of equine IL10 construct is a key step toward translational relevance
Key Findings
- •AAV8-Equine-IL10 gene therapy significantly reduced clinical inflammatory scores and aqueous humor cell counts in treated rats compared to controls on days 10, 12, and 14 post-EAU induction
- •Histopathologic cellular infiltration scores were significantly lower in AAV8-Equine-IL10 treated rats across both low and high dose groups
- •A single intravitreal injection of AAV8-Equine-IL10 was well-tolerated and produced dose-dependent cDNA expression in ciliary body, retina, cornea, and optic nerve
- •Therapeutic efficacy was demonstrated at both low (2.4×10⁹ vg) and high (2.4×10¹⁰ vg) vector doses in the rat EAU model