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Xiaomin Zhang, Zhihui Zhang, Shuang Chen, Nu Chen, Jian-Xing (Jay) Ma, Xiaorong Li; Targeting PEDF for the treatment of experimental autoimmune uveitis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):794.
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© ARVO (1962-2015); The Authors (2016-present)
Pigment epithelium-derived factor (PEDF) is emerging as a new target for treating many ocular diseases such as diabetic retinopathy and age-related macular degeneration, but the potential role of PEDF in the pathogenesis of uveitis is unclear. To address this issue, we studied experimental autoimmune uveitis (EAU) in wild-type (WT) and PEDF knockout (KO) mice.
After EAU induction, we compared disease severity in WT and PEDF KO mice using indirect ophthalmoscopy, spectral-domain optical coherence tomography and histopathological analysis. We also explored the underlying mechanism by examining T cell responses in ex vivo antigen-specific recall assays and in vitro T cell priming assays using bone-marrow-derived dendritic cells, splenic dendritic cells, and T cells from WT or PEDF mice. Uveitogenic T cells from WT and PEDF KO mice were adoptively transferred into WT naïve mice to confirm the impact of PEDF on T cells.
We found that PEDF KO mice developed much less severe retinal inflammation than WT mice. We also demonstrated reduced autoreactive T cell responses and decreased retinal T cell infiltration. Furthermore, we confirmed the impaired uveitogenic capacity of T cells from these mice in an adoptive transfer experiment.
Our results strongly suggest that PEDF play a previously unknown but pivotal role in autoimmune uveitis, and may be a promising new treatment target for this human disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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