title: Stanniocalcin-1 rescued photoreceptor degeneration in two rat models of inherited retinal degeneration.
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).
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, Texas 76502, USA.
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Roddy
authors.forename: Robert H
authors.initials: RH
authors.lastname: Rosa
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Oh
authors.forename: Joni H
authors.initials: JH
authors.lastname: Ylostalo
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Bartosh
authors.forename: Hosoon
authors.initials: H
authors.lastname: Choi
authors.forename: Ryang Hwa
authors.initials: RH
authors.lastname: Lee
authors.forename: Douglas
authors.initials: D
authors.lastname: Yasumura
authors.forename: Kelly
authors.initials: K
authors.lastname: Ahern
authors.forename: Gregory
authors.initials: G
authors.lastname: Nielsen
authors.forename: Michael T
authors.initials: MT
authors.lastname: Matthes
authors.forename: Matthew M
authors.initials: MM
authors.lastname: LaVail
authors.forename: Darwin J
authors.initials: DJ
authors.lastname: Prockop
mesh_terms: D000818:Animals; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008268:Macular Degeneration / Q000188:drug therapy; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000188:drug therapy; D000071246:Uncoupling Protein 2
chemical_list: D006023:Glycoproteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C051795:teleocalcin