AAV-mediated STC-1 expression mitigates neuroinflammation and preserves visual function in degenerative retinopathy.

BACKGROUND

Retinal degeneration (RD) is a chronic retinopathy that characterized by the progressive photoreceptor apoptosis and visual impairments. However, due to the complicated pathogenesis of RD, there is no effective treatment at present. This study intends to verify the therapeutic effect and mechanism of stanniocalcin-1 (STC-1) in the sodium iodate (NaIO3)-induced RD mouse model.

METHODS

The pAAV2/8-Stc1 vector was established and delivered into the vitreous cavity of RD mouse model. Subsequently, these treated mice were subjected to a series of functional and morphological assay.

RESULTS

Pervasive neuroinflammation reaction and oxidative stress occurred in the retinas of RD model. Intravitreal injection of pAAV2/8-Stc1 vector enabled the stable STC-1 expression in the retinas. AAV-mediated STC-1 overexpression could preserve the retinal structure and enhance the photoreceptor survival effectively. Fundus photography showed the distribution of retinal vessel was clear, and the severity of lesions was relieved. Particularly, these morphological benefits could yield significant improvements in visual functionality, as evidenced by both behavioral tests and multifocal electroretinogram (mf-ERG) evaluations. Mechanism study showed that STC-1 alleviated the oxidative stress, inhibited the neuroglia activation, and mitigated the release of pro-inflammatory cytokines through CX3CL1/CX3CR1/NF-κB axis.

CONCLUSIONS

This research unveils a robust correlation between the photoreceptor vitality and the STC-1 expression in RD model. The AAV mediated STC-1 over-expression can be developed into a promising therapeutic approach for degenerative retinopathy.