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AAV2-mediated combined subretinal delivery of IFN-α and IL-4 reduces the severity of experimental autoimmune uveoretinitis.

Tian L, Lei B, Shao J, Wei L, Kijlstra A, Yang P - PLoS ONE (2012)

Bottom Line: IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically.AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α.The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone.

View Article: PubMed Central - PubMed

Affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China.

ABSTRACT
We previously showed that adeno-associated virus 2 (AAV2) mediated subretinal delivery of human interferon-alpha (IFN-α) could effectively inhibit experimental autoimmune uveoretinitis (EAU). In this study we investigated whether subretinal injection of both AVV2.IFN-α and AAV2.IL-4 had a stronger inhibition on EAU activity. B10RIII mice were subretinally injected with AAV2.IFN-α alone (1.5×10(7) vg), AAV2.IL-4 alone (3.55×10(7) vg), and AAV2.IFN-α combined with AAV2.IL-4. PBS, AAV2 vector encoding green fluorescent protein (AAV2.GFP) (5×10(7) vg) was subretinally injected as a control. IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically. AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α. The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone. There was no difference concerning DTH (delayed-type hypersensitivity) reaction, lymphocyte proliferation and IL-17 production among the investigated treatment groups, suggesting that local retinal gene delivery did not affect the systemic immune response.

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Related in: MedlinePlus

Scheme of the AAV2 vector construct.The transgene is under the control of a CMV promoter and followed by BGH poly (A). The expression cassette is flanked by ITRs. CMV promoter, human cytomegalovirus immediate early promoter; hIFN-α, human interferon-alpha; BGH poly (A), BGH poly-adenylation signal; ITR, AAV2 inverted terminal repeats.
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pone-0037995-g001: Scheme of the AAV2 vector construct.The transgene is under the control of a CMV promoter and followed by BGH poly (A). The expression cassette is flanked by ITRs. CMV promoter, human cytomegalovirus immediate early promoter; hIFN-α, human interferon-alpha; BGH poly (A), BGH poly-adenylation signal; ITR, AAV2 inverted terminal repeats.

Mentions: The IFN-α or IL-4 gene was driven by the human cytomegalovirus (CMV) promoter and was followed by a BGH poly(A) signal (Fig. 1). Titers of recombinant vectors used were 3×1010 vg/ml and 7.1×1010 vg/ml for AAV2.IFN-α and AAV2.IL-4, respectively. AAV2.GFP was used as a vector control (1×1011 vg/ml).


AAV2-mediated combined subretinal delivery of IFN-α and IL-4 reduces the severity of experimental autoimmune uveoretinitis.

Tian L, Lei B, Shao J, Wei L, Kijlstra A, Yang P - PLoS ONE (2012)

Scheme of the AAV2 vector construct.The transgene is under the control of a CMV promoter and followed by BGH poly (A). The expression cassette is flanked by ITRs. CMV promoter, human cytomegalovirus immediate early promoter; hIFN-α, human interferon-alpha; BGH poly (A), BGH poly-adenylation signal; ITR, AAV2 inverted terminal repeats.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369876&req=5

pone-0037995-g001: Scheme of the AAV2 vector construct.The transgene is under the control of a CMV promoter and followed by BGH poly (A). The expression cassette is flanked by ITRs. CMV promoter, human cytomegalovirus immediate early promoter; hIFN-α, human interferon-alpha; BGH poly (A), BGH poly-adenylation signal; ITR, AAV2 inverted terminal repeats.
Mentions: The IFN-α or IL-4 gene was driven by the human cytomegalovirus (CMV) promoter and was followed by a BGH poly(A) signal (Fig. 1). Titers of recombinant vectors used were 3×1010 vg/ml and 7.1×1010 vg/ml for AAV2.IFN-α and AAV2.IL-4, respectively. AAV2.GFP was used as a vector control (1×1011 vg/ml).

Bottom Line: IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically.AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α.The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone.

View Article: PubMed Central - PubMed

Affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China.

ABSTRACT
We previously showed that adeno-associated virus 2 (AAV2) mediated subretinal delivery of human interferon-alpha (IFN-α) could effectively inhibit experimental autoimmune uveoretinitis (EAU). In this study we investigated whether subretinal injection of both AVV2.IFN-α and AAV2.IL-4 had a stronger inhibition on EAU activity. B10RIII mice were subretinally injected with AAV2.IFN-α alone (1.5×10(7) vg), AAV2.IL-4 alone (3.55×10(7) vg), and AAV2.IFN-α combined with AAV2.IL-4. PBS, AAV2 vector encoding green fluorescent protein (AAV2.GFP) (5×10(7) vg) was subretinally injected as a control. IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically. AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α. The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone. There was no difference concerning DTH (delayed-type hypersensitivity) reaction, lymphocyte proliferation and IL-17 production among the investigated treatment groups, suggesting that local retinal gene delivery did not affect the systemic immune response.

Show MeSH
Related in: MedlinePlus