September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Neuropeptide Y induces neuroprotective effects and neurite outgrowth in rat retinal cell cultures
Author Affiliations & Notes
  • Anders Tolstrup Christiansen
    Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
    Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
  • Casper René Gøtzsche
    Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
  • Laure Plantard
    Core Facility for Integrated Microscopy, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Kristian Klemp
    Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  • Morten D De La Cour
    Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  • Jens F Kiilgaard
    Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  • David Paul Drucker Woldbye
    Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
  • Footnotes
    Commercial Relationships   Anders Tolstrup Christiansen, RetiCare (P); Casper Gøtzsche, RetiCare (P); Laure Plantard, None; Kristian Klemp, RetiCare (P); Morten De La Cour, None; Jens Kiilgaard, None; David Woldbye, RetiCare (P)
  • Footnotes
    Support  Fight for Sight Denmark, The Danish Eye Research Foundation, and The Synoptik Foundation
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4399. doi:
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      Anders Tolstrup Christiansen, Casper René Gøtzsche, Laure Plantard, Kristian Klemp, Morten D De La Cour, Jens F Kiilgaard, David Paul Drucker Woldbye; Neuropeptide Y induces neuroprotective effects and neurite outgrowth in rat retinal cell cultures. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4399.

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

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Abstract

Purpose : Neuropeptide Y (NPY) has been shown to exert neuroprotective effects in the brain and lately also in retinal tissue. We further explored the neuroprotective effects of NPY by studying actions of NPY on glutamate-induced toxicity in rat retinal cell cultures. In addition, we also for the first time examined effects of NPY on neurite outgrowth in retinal cells, a neuroplastic effect that might contribute to recovery of retinal cells after injury.

Methods : Rat retinal cell cultures were prepared from newborn Wistar rats (P3-P5). For neuroprotection cultures were cultivated for one week (n=11). Cell death was induced by addition of glutamate (300 μM) for 24h added 1h after pretreatment with NPY. To evaluate the specific NPY receptors involved in neuroprotection, cultures were pretreated with Y1, Y2, or Y5 receptor antagonists (n=5). Cell death was evaluated by a propidium iodide (PI) assay and calculated as a ratio of PI positive cells to total cell numbers. For neurite outgrowth, cultures were grown for 24h with NPY, immunostained with anti-GAP43 neuron-specific antibody and evaluated using specially developed software (n=4). Data were analyzed with GraphPad Prism software using repeated measures one-way ANOVA with Bonferroni-adjusted post-hoc tests.

Results : NPY induced neuroprotective effects in a dose-dependent manner, reaching significant levels at 0.3 and 1 μM NPY with maximal protection found with 1 μM (0.3 μM: p<0.05; 1 μM: p<0.01). This neuroprotective effect was inhibited by addition of selective NPY receptor antagonists and completely abolished by addition of all three antagonists (NPY vs NPY+Y1-Y2-Y5-antagonists: p<0.05). Addition of NPY antagonists suggested that the neuroprotective effect was mainly mediated via Y2 and Y5 receptors. [R1] Moreover, NPY induced neurite outgrowth at concentrations of 1 μM and 10 μM NPY with most pronounced effects seen at 10 μM (1 μM: p<0.05; 10 μM: p<0.05).

Conclusions : Consistent with previous work, we found that NPY exerts neuroprotective effects in rat retinal cell cultures predominantly mediated via Y2 and Y5 receptors. NPY was also for the first time found to stimulate neurite outgrowth in retinal cells. These neuroprotective and neuroplastic effects of NPY indicate that NPY could play a role as a neurotrophic and neuroprotective agent in future treatment of retinal diseases.

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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