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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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Systemic IRBP-specific immune responses in each group.DTH responses were elicited on day 19 of EAU and evaluated on day 21. Data show no significant difference of ear swelling among all the tested groups (p>0.05) (a). IRBP-specific lymphocyte proliferation (b) and IL-17 production in vitro (c) show no significant difference among the five tested groups (P>0.05). Results are presented as mean±standard deviation. 5–6 animals per group were used and each experiment was performed three times.
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pone-0037995-g005: Systemic IRBP-specific immune responses in each group.DTH responses were elicited on day 19 of EAU and evaluated on day 21. Data show no significant difference of ear swelling among all the tested groups (p>0.05) (a). IRBP-specific lymphocyte proliferation (b) and IL-17 production in vitro (c) show no significant difference among the five tested groups (P>0.05). Results are presented as mean±standard deviation. 5–6 animals per group were used and each experiment was performed three times.

Mentions: DTH reactions in vivo and lymphocyte responses to IRBP161–180in vitro were assayed to evaluate the impact of AAV2 vector subretinal injection on the systemic immune response. Results showed that there was no significant difference in the DTH reactions against IRBP between AAV2.IL-4 injected mice, AAV2.IFN-α injected mice, AAV2.IL-4 combined with AAV2.IFN-α treated mice, AAV2.GFP injected control mice and PBS injected controls (p>0.05) (Fig. 5 a).


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)

Systemic IRBP-specific immune responses in each group.DTH responses were elicited on day 19 of EAU and evaluated on day 21. Data show no significant difference of ear swelling among all the tested groups (p>0.05) (a). IRBP-specific lymphocyte proliferation (b) and IL-17 production in vitro (c) show no significant difference among the five tested groups (P>0.05). Results are presented as mean±standard deviation. 5–6 animals per group were used and each experiment was performed three times.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0037995-g005: Systemic IRBP-specific immune responses in each group.DTH responses were elicited on day 19 of EAU and evaluated on day 21. Data show no significant difference of ear swelling among all the tested groups (p>0.05) (a). IRBP-specific lymphocyte proliferation (b) and IL-17 production in vitro (c) show no significant difference among the five tested groups (P>0.05). Results are presented as mean±standard deviation. 5–6 animals per group were used and each experiment was performed three times.
Mentions: DTH reactions in vivo and lymphocyte responses to IRBP161–180in vitro were assayed to evaluate the impact of AAV2 vector subretinal injection on the systemic immune response. Results showed that there was no significant difference in the DTH reactions against IRBP between AAV2.IL-4 injected mice, AAV2.IFN-α injected mice, AAV2.IL-4 combined with AAV2.IFN-α treated mice, AAV2.GFP injected control mice and PBS injected controls (p>0.05) (Fig. 5 a).

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