September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A GSK-3b modulator delays photoreceptor cell death and preserves visual function in the rd10 mouse model of retinitis pigmentosa.
Author Affiliations & Notes
  • Catalina Hernandez- Sanchez
    Molecular and Cellular Medicine, Centro De Investigaciones Biologicas (CSIC), Madrid, Spain
  • Beatriz Villarejo
    Molecular and Cellular Medicine, Centro De Investigaciones Biologicas (CSIC), Madrid, Spain
  • Josefa Zaldivar
    Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain
  • Miguel Marchena
    Molecular and Cellular Medicine, Centro De Investigaciones Biologicas (CSIC), Madrid, Spain
  • Carmen Gil
    Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain
  • Pedro de la Villa
    Universidad de Alcalá de Henares, Alcalá de Henares, Spain
  • Ana Martínez
    Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain
  • Enrique J De La Rosa
    Molecular and Cellular Medicine, Centro De Investigaciones Biologicas (CSIC), Madrid, Spain
  • Footnotes
    Commercial Relationships   Catalina Hernandez- Sanchez, None; Beatriz Villarejo, None; Josefa Zaldivar, None; Miguel Marchena, None; Carmen Gil, ANKAR Pharma (I), ANKAR Pharma (P); Pedro de la Villa, None; Ana Martínez, ANKAR Pharma (I), ANKAR Pharma (P); Enrique De La Rosa, None
  • Footnotes
    Support  SAF2013-41059-R
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4396. doi:
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      Catalina Hernandez- Sanchez, Beatriz Villarejo, Josefa Zaldivar, Miguel Marchena, Carmen Gil, Pedro de la Villa, Ana Martínez, Enrique J De La Rosa; A GSK-3b modulator delays photoreceptor cell death and preserves visual function in the rd10 mouse model of retinitis pigmentosa.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4396.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies that lead to blindness. Photoreceptor cell death, reactive gliosis and retinal inflammation are common features in animal models of the disease. The enzyme Glycogen Synthase Kinase-3 Beta (GSK-3β) is involved in inflammatory processes associated to diverse neurodegenerative pathologies. The aim of our study is to test in the rd10 mouse whether the GSK-3β inhibitor VP3.15 (a small heterocyclic molecule) is a potential therapeutic treatment for RP.

Methods : Ex vivo studies: rd10 retinas at postnatal day 23 (P23) were placed in organotypic culture and treated with the VP3.15 GSK-3β modulator. Photoreceptor cell death was analyzed TUNEL. In vivo studies: VP3.15 was injected intraperitoneally into rd10 mice from P15 to P45. Visual function was evaluated by ERG recording and retinal structure was visualized by immunohistochemistry in cryosections. The expression of pro-inflammatory genes was analyzed by RT-qPCR.

Results : The GSK-3β inhibitor decreased by 50% photoreceptor cell death ex vivo. Moreover, intraperitoneal administration of VP3.15 to rd10 mice preserved photoreceptor cell number and prevented microglial infiltration at P23, decreased pro-inflammatory TNF-α and IL-1β, as well as GFAP gene expression at P23, and improved visual function up to P46.

Conclusions : GSK-3β inhibitors may constitute a therapeutic strategy for the treatment of Retinitis Pigmentosa.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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