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Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia

Kyhn, Maria Voss; Klassen, Henry; Englund Johansson, Ulrica LU ; Warfvinge, Karin LU ; Lavik, Erin; Kiilgaard, Jens F.; Prause, Jan Ulrik; Scherfig, Erik; Young, Michael and la Cour, Morten (2009) In Experimental Eye Research 89(6). p.1012-1020
Abstract
This study investigates whether intravitreal administration of glial cell line-derived neurotrophic factor (GDNF) enhances survival of NeuN positive retinal cells in a porcine model of retinal ischemia. 16 pigs were subjected to an ischemic insult where intraocular pressure was maintained at 5 mmHg below mean arterial blood pressure for 2 h. The mean IOP during the ischemic insult was 79.5 mmHg (s.e.m. 2.1 mmHg, n = 15). Three days after the insult the pigs received an intravitreal injection of GDNF microspheres or blank microspheres. The pigs were evaluated by way of multifocal electroretinography (mfERG), quantification of NeuN positive cells and evaluation of the degree of retinal perivasculitis and inflammation 6 weeks after the... (More)
This study investigates whether intravitreal administration of glial cell line-derived neurotrophic factor (GDNF) enhances survival of NeuN positive retinal cells in a porcine model of retinal ischemia. 16 pigs were subjected to an ischemic insult where intraocular pressure was maintained at 5 mmHg below mean arterial blood pressure for 2 h. The mean IOP during the ischemic insult was 79.5 mmHg (s.e.m. 2.1 mmHg, n = 15). Three days after the insult the pigs received an intravitreal injection of GDNF microspheres or blank microspheres. The pigs were evaluated by way of multifocal electroretinography (mfERG), quantification of NeuN positive cells and evaluation of the degree of retinal perivasculitis and inflammation 6 weeks after the insult. In the post-injection eyes (days 14, 28 and 42), the ratios of the iN1 and the iP2 amplitudes were 0.10 (95% CI: 0.05-0.15) and 0.09 (95% CI: 0.04-0.16) in eyes treated with blank microspheres, and 0.24 (95% CI: 0.18-0.32) and 0.23 (95% CI: 0.15-0.33) in eyes treated with GDNF microspheres. These differences were statistically significant (P < 0.05). The number of NeuN positive cells in the area of the visual streak area was significantly higher in eyes injected with GDNF microspheres compared to eyes injected with blank microspheres. In eyes injected with GDNF microspheres the ganglion cell count was 9.5/field (s.e.m.: 2.1, n = 8), in eyes injected with blank microspheres it was 3.5/field (s.e.m.: 1.2, n = 7). This difference was statistically significant (P < 0.05). There was also a significant difference (P < 0.01) in the degree of perivasculiitis between GDNF treated eyes (median perivasculitis score 1.5) and blank treated eyes (median perivasculitis score 3.0). In conclusion, injection of GDNF microspheres 3 days after an ischemic insult results in functional and morphological rescue of NeuN positive cells in a porcine model of acute ocular ischemia. (C) 2009 Elsevier Ltd. All rights reserved. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
keywords
ocular perfusion pressure, perfusion pressure, low, retinal ischemia, induced components, pig, multifocal ERG, neuroprotection, GDNF, glial cell line-derived neurotropic factor
in
Experimental Eye Research
volume
89
issue
6
pages
1012 - 1020
publisher
Elsevier
external identifiers
  • wos:000272106000025
  • scopus:70350714242
ISSN
0014-4835
DOI
10.1016/j.exer.2009.08.014
language
English
LU publication?
yes
id
fa2827a9-bf07-440d-a24a-a6fcd6729739 (old id 1518419)
date added to LUP
2010-01-13 08:45:41
date last changed
2017-11-05 03:46:46
@article{fa2827a9-bf07-440d-a24a-a6fcd6729739,
  abstract     = {This study investigates whether intravitreal administration of glial cell line-derived neurotrophic factor (GDNF) enhances survival of NeuN positive retinal cells in a porcine model of retinal ischemia. 16 pigs were subjected to an ischemic insult where intraocular pressure was maintained at 5 mmHg below mean arterial blood pressure for 2 h. The mean IOP during the ischemic insult was 79.5 mmHg (s.e.m. 2.1 mmHg, n = 15). Three days after the insult the pigs received an intravitreal injection of GDNF microspheres or blank microspheres. The pigs were evaluated by way of multifocal electroretinography (mfERG), quantification of NeuN positive cells and evaluation of the degree of retinal perivasculitis and inflammation 6 weeks after the insult. In the post-injection eyes (days 14, 28 and 42), the ratios of the iN1 and the iP2 amplitudes were 0.10 (95% CI: 0.05-0.15) and 0.09 (95% CI: 0.04-0.16) in eyes treated with blank microspheres, and 0.24 (95% CI: 0.18-0.32) and 0.23 (95% CI: 0.15-0.33) in eyes treated with GDNF microspheres. These differences were statistically significant (P &lt; 0.05). The number of NeuN positive cells in the area of the visual streak area was significantly higher in eyes injected with GDNF microspheres compared to eyes injected with blank microspheres. In eyes injected with GDNF microspheres the ganglion cell count was 9.5/field (s.e.m.: 2.1, n = 8), in eyes injected with blank microspheres it was 3.5/field (s.e.m.: 1.2, n = 7). This difference was statistically significant (P &lt; 0.05). There was also a significant difference (P &lt; 0.01) in the degree of perivasculiitis between GDNF treated eyes (median perivasculitis score 1.5) and blank treated eyes (median perivasculitis score 3.0). In conclusion, injection of GDNF microspheres 3 days after an ischemic insult results in functional and morphological rescue of NeuN positive cells in a porcine model of acute ocular ischemia. (C) 2009 Elsevier Ltd. All rights reserved.},
  author       = {Kyhn, Maria Voss and Klassen, Henry and Englund Johansson, Ulrica and Warfvinge, Karin and Lavik, Erin and Kiilgaard, Jens F. and Prause, Jan Ulrik and Scherfig, Erik and Young, Michael and la Cour, Morten},
  issn         = {0014-4835},
  keyword      = {ocular perfusion pressure,perfusion pressure,low,retinal ischemia,induced components,pig,multifocal ERG,neuroprotection,GDNF,glial cell line-derived neurotropic factor},
  language     = {eng},
  number       = {6},
  pages        = {1012--1020},
  publisher    = {Elsevier},
  series       = {Experimental Eye Research},
  title        = {Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia},
  url          = {http://dx.doi.org/10.1016/j.exer.2009.08.014},
  volume       = {89},
  year         = {2009},
}