10.5061/DRYAD.Q83BK3JKQ
Gilger, Brian
0000-0002-7771-9166
North Carolina State University
AAV gene therapy encoding equine IL10
Dryad
dataset
2022
FOS: Biological sciences
experimental autoimmune uveitis
Adeno-associated virus
AAV
Gene therapy
IL10
intravitreal
equine recurrent uveitis
2022-08-02T00:00:00Z
2022-08-02T00:00:00Z
en
https://doi.org/10.5281/zenodo.6430350
275329 bytes
4
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Equine recurrent uveitis (ERU) is a spontaneous, painful, and vision
threatening disease affecting up to 25% of equine populations worldwide.
Current treatments of ERU are non-specific and have many side effects
which limits them to short-term use. In order to develop an effective
therapy for ERU, we investigated the use of adeno-associated virus (AAV)
gene therapy, exploiting a natural immune tolerance mechanism induced by
equine interleukin-10 (Equine-IL10). The purpose of this study was to
evaluate the therapeutic efficacy of a single intravitreal (IVT) dose of
AAV8-Equine-IL10 gene therapy for inhibition of experimental autoimmune
uveitis (EAU) in rats. Each rat was dosed intravitreally (IVT) in both
eyes with either balanced salt solution (BSS) (control;
n=4), AAV8-Equine-IL10 at a low dose (2.4x109 vg; n=5) or high dose
(2.4x1010 vg; n=5). EAU was induced in all groups of rats 7 days after IVT
injections and euthanized 21 days post-injection. Ophthalmic examination
and aqueous humor (AH) cell counts were recorded with the observer blinded
to the treatment groups. Histopathology and qPCR were performed on
selected ocular tissues. Data presented herein demonstrate that
AAV8-Equine-IL10 treated rats exhibited a significant decrease in clinical
inflammatory scores and AH cell counts compared to BSS-treated EAU eyes on
days 10, 12 and 14 post EAU induction at both administered vector
doses. Mean cellular histologic infiltrative scores were also
significantly less in AAV8-Equine-IL10 dosed rats compared to the BSS
group. Intravitreal injection of AAV8-Equine-IL10 resulted in Equine-IL10
cDNA expression in the ciliary body, retina, cornea, and optic nerve in a
dose-dependent manner. A single IVT injection of AAV8-Equine-IL10
appeared to be well-tolerated and inhibited EAU even at the lowest
administered dose. These results demonstrate safety and efficacy of
AAV8-Equine-IL10 to prevent EAU and support continued exploration of AAV
gene therapy for the treatment of equine and perhaps human recurrent
uveitis.