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Neuropeptide Y treatment induces retinal vasoconstriction and causes functional and histological retinal damage in a porcine ischaemia model

Christiansen, Anders T.; Sørensen, Nina B.; Haanes, Kristian A.; Blixt, Frank W. LU ; la Cour, Morten; Warfvinge, Karin LU ; Klemp, Kristian; Woldbye, David P.D. and Kiilgaard, Jens F. (2018) In Acta Ophthalmologica 96(8). p.812-820
Abstract

Purpose: To investigate the effects of intravitreal neuropeptide Y (NPY) treatment following acute retinal ischaemia in an in vivo porcine model. In addition, we evaluated the vasoconstrictive potential of NPY on porcine retinal arteries ex vivo. Methods: Twelve pigs underwent induced retinal ischaemia by elevated intraocular pressure clamping the ocular perfusion pressure at 5 mmHg for 2 hr followed by intravitreal injection of NPY or vehicle. After 4 weeks, retinas were evaluated functionally by standard and global-flash multifocal electroretinogram (mfERG) and histologically by thickness of retinal layers and number of ganglion cells. Additionally, the vasoconstrictive effects of NPY and its involved receptors were tested using wire... (More)

Purpose: To investigate the effects of intravitreal neuropeptide Y (NPY) treatment following acute retinal ischaemia in an in vivo porcine model. In addition, we evaluated the vasoconstrictive potential of NPY on porcine retinal arteries ex vivo. Methods: Twelve pigs underwent induced retinal ischaemia by elevated intraocular pressure clamping the ocular perfusion pressure at 5 mmHg for 2 hr followed by intravitreal injection of NPY or vehicle. After 4 weeks, retinas were evaluated functionally by standard and global-flash multifocal electroretinogram (mfERG) and histologically by thickness of retinal layers and number of ganglion cells. Additionally, the vasoconstrictive effects of NPY and its involved receptors were tested using wire myographs and NPY receptor antagonists on porcine retinal arteries. Results: Intravitreal injection of NPY after induced ischaemia caused a significant reduction in the mean induced component (IC) amplitude ratio (treated/normal eye) compared to vehicle-treated eyes. This reduction was accompanied by histological damage, where NPY treatment reduced the mean thickness of inner retinal layers and number of ganglion cells. In retinal arteries, NPY-induced vasoconstriction to a plateau of approximately 65% of potassium-induced constriction. This effect appeared to be mediated via Y1 and Y2, but not Y5. Conclusion: In seeming contrast to previous in vitro studies, intravitreal NPY treatment caused functional and histological damage compared to vehicle after a retinal ischaemic insult. Furthermore, we showed for the first time that NPY induces Y1- and Y2- but not Y5-mediated vasoconstriction in retinal arteries. This constriction could explain the worsening in vivo effect induced by NPY treatment following an ischaemic insult and suggests that future studies on exploring the neuroprotective effects of NPY might focus on other receptors than Y1 and Y2.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
multifocal electroretinogram, neuropeptide Y, neuropeptide Y receptors, neuroprotection, retina, swine, vasoconstriction
in
Acta Ophthalmologica
volume
96
issue
8
pages
812 - 820
publisher
Wiley-Blackwell
external identifiers
  • scopus:85053448239
ISSN
1755-375X
DOI
10.1111/aos.13806
language
English
LU publication?
yes
id
cc4cce15-4bd3-4a46-b366-c99b48aa4a62
date added to LUP
2018-10-23 09:42:27
date last changed
2019-01-14 17:12:03
@article{cc4cce15-4bd3-4a46-b366-c99b48aa4a62,
  abstract     = {<p>Purpose: To investigate the effects of intravitreal neuropeptide Y (NPY) treatment following acute retinal ischaemia in an in vivo porcine model. In addition, we evaluated the vasoconstrictive potential of NPY on porcine retinal arteries ex vivo. Methods: Twelve pigs underwent induced retinal ischaemia by elevated intraocular pressure clamping the ocular perfusion pressure at 5 mmHg for 2 hr followed by intravitreal injection of NPY or vehicle. After 4 weeks, retinas were evaluated functionally by standard and global-flash multifocal electroretinogram (mfERG) and histologically by thickness of retinal layers and number of ganglion cells. Additionally, the vasoconstrictive effects of NPY and its involved receptors were tested using wire myographs and NPY receptor antagonists on porcine retinal arteries. Results: Intravitreal injection of NPY after induced ischaemia caused a significant reduction in the mean induced component (IC) amplitude ratio (treated/normal eye) compared to vehicle-treated eyes. This reduction was accompanied by histological damage, where NPY treatment reduced the mean thickness of inner retinal layers and number of ganglion cells. In retinal arteries, NPY-induced vasoconstriction to a plateau of approximately 65% of potassium-induced constriction. This effect appeared to be mediated via Y1 and Y2, but not Y5. Conclusion: In seeming contrast to previous in vitro studies, intravitreal NPY treatment caused functional and histological damage compared to vehicle after a retinal ischaemic insult. Furthermore, we showed for the first time that NPY induces Y1- and Y2- but not Y5-mediated vasoconstriction in retinal arteries. This constriction could explain the worsening in vivo effect induced by NPY treatment following an ischaemic insult and suggests that future studies on exploring the neuroprotective effects of NPY might focus on other receptors than Y1 and Y2.</p>},
  author       = {Christiansen, Anders T. and Sørensen, Nina B. and Haanes, Kristian A. and Blixt, Frank W. and la Cour, Morten and Warfvinge, Karin and Klemp, Kristian and Woldbye, David P.D. and Kiilgaard, Jens F.},
  issn         = {1755-375X},
  keyword      = {multifocal electroretinogram,neuropeptide Y,neuropeptide Y receptors,neuroprotection,retina,swine,vasoconstriction},
  language     = {eng},
  month        = {01},
  number       = {8},
  pages        = {812--820},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Ophthalmologica},
  title        = {Neuropeptide Y treatment induces retinal vasoconstriction and causes functional and histological retinal damage in a porcine ischaemia model},
  url          = {http://dx.doi.org/10.1111/aos.13806},
  volume       = {96},
  year         = {2018},
}