Stanniocalcin-1 rescued photoreceptor degeneration in two rat models of inherited retinal degeneration.
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abstract
Oxidative stress and photoreceptor apoptosis are prominent features of many forms of retinal degeneration (RD) for which there are currently no effective therapies. We previously observed that mesenchymal stem/stromal cells reduce apoptosis by being activated to secrete stanniocalcin-1 (STC-1), a multifunctional protein that reduces oxidative stress by upregulating mitochondrial uncoupling protein-2 (UCP-2). Therefore, we tested the hypothesis that intravitreal injection of STC-1 can rescue photoreceptors. We first tested STC-1 in the rhodopsin transgenic rat characterized by rapid photoreceptor loss. Intravitreal STC-1 decreased the loss of photoreceptor nuclei and transcripts and resulted in measurable retinal function when none is otherwise present in this rapid degeneration. We then tested STC-1 in the Royal College of Surgeons (RCS) rat characterized by a slower photoreceptor degeneration. Intravitreal STC-1 reduced the number of pyknotic nuclei in photoreceptors, delayed the loss of photoreceptor transcripts, and improved function of rod photoreceptors. Additionally, STC-1 upregulated UCP-2 and decreased levels of two protein adducts generated by reactive oxygen species (ROS). Microarrays from the two models demonstrated that STC-1 upregulated expression of a similar profile of genes for retinal development and function. The results suggested that intravitreal STC-1 is a promising therapy for various forms of RD including retinitis pigmentosa and atrophic age-related macular degeneration (AMD).
Roddy, G. W., Rosa, R. H., Oh, J. Y., Ylostalo, J. H., Bartosh, T. J., Choi, H., ... Prockop, D. J.
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Roddy, Gavin W||Rosa, Robert H||Oh, Joo Youn||Ylostalo, Joni H||Bartosh, Thomas J||Choi, Hosoon||Lee, Ryang Hwa||Yasumura, Douglas||Ahern, Kelly||Nielsen, Gregory||Matthes, Michael T||LaVail, Matthew M||Prockop, Darwin J
