Long-term photoreceptor rescue in two rodent models of retinitis pigmentosa by adeno-associated virus delivery of Stanniocalcin-1. Academic Article uri icon

abstract

  • Retinal degenerations, including age-related macular degeneration and the retinitis pigmentosa family of diseases, are among the leading causes of legal blindness in the United States. We previously found that Stanniocalcin-1 (STC-1) reduced photoreceptor loss in the S334ter-3 and Royal College of Surgeons rat models of retinal degeneration. The results were attributed in part to a reduction in oxidative stress. Herein, we tested the hypothesis that long-term delivery of STC-1 would provide therapeutic rescue in more chronic models of retinal degeneration. To achieve sustained delivery, we produced an adeno-associated virus (AAV) construct to express STC-1 (AAV-STC-1) under the control of a retinal ganglion cell targeting promoter human synapsin 1 (hSYN1). AAV-STC-1 was injected intravitreally into the P23H-1 and S334ter-4 rhodopsin transgenic rats at postnatal day 10. Tissues were collected at postnatal day 120 for confirmation of STC-1 overexpression and histologic and molecular analysis. Electroretinography (ERG) was performed in a cohort of animals at that time. Overexpression of STC-1 resulted in a significant preservation of photoreceptors as assessed by outer nuclear thickness in the P23H-1 (P<0.05) and the S334ter-4 (P<0.005) models compared to controls. Additionally, retinal function was significantly improved in the P23H-1 model with overexpressed STC-1 as assessed by ERG analysis (scotopic b-wave P<0.005 and photopic b-wave P<0.05). Microarray analysis identified common downstream gene expression changes that occurred in both models. Genes of interest based on their function were selected for validation by quantitative real-time PCR and were significantly increased in the S334ter-4 model.

published proceedings

  • Exp Eye Res

altmetric score

  • 3.25

author list (cited authors)

  • Roddy, G. W., Yasumura, D., Matthes, M. T., Alavi, M. V., Boye, S. L., Rosa, R. H., ... LaVail, M. M.

citation count

  • 10

complete list of authors

  • Roddy, Gavin W||Yasumura, Douglas||Matthes, Michael T||Alavi, Marcel V||Boye, Sanford L||Rosa, Robert H||Fautsch, Michael P||Hauswirth, William W||LaVail, Matthew M

publication date

  • January 2017