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

Maria Voss Kyhn; Henry Klassen; Ulrica Englund Johansson; Karin Warfvinge; Erin Lavik; Jens F Kiilgaard; Jan Ulrik Prause; Erik Scherfig; Michael Young; Morten la Cour; Maria Voss Kyhn; Henry Klassen; Ulrica Englund Johansson; Karin Warfvinge; Erin Lavik; Jens F Kiilgaard; Jan Ulrik Prause; Erik Scherfig; Michael Young; Morten la Cour

doi:10.1016/j.exer.2009.08.014

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

Maria Voss Kyhn, Henry Klassen, Ulrica Englund Johansson, Karin Warfvinge, Erin Lavik, Jens F Kiilgaard, Jan Ulrik Prause, Erik Scherfig, Michael Young, Morten la Cour, Maria Voss Kyhn, Henry Klassen, Ulrica Englund Johansson, Karin Warfvinge, Erin Lavik, Jens F Kiilgaard, Jan Ulrik Prause, Erik Scherfig, Michael Young, Morten la Cour

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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 < 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.

Original language	English
Journal	Experimental Eye Research
Volume	89
Issue number	6
Pages (from-to)	1012-20
Number of pages	9
ISSN	0014-4835
DOIs	https://doi.org/10.1016/j.exer.2009.08.014 https://doi.org/10.1016/j.exer.2009.08.014
Publication status	Published - 1 Dec 2009

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Kyhn, M. V., Klassen, H., Johansson, U. E., Warfvinge, K., Lavik, E., Kiilgaard, J. F., Prause, J. U., Scherfig, E., Young, M., la Cour, M., Kyhn, M. V., Klassen, H., Johansson, U. E., Warfvinge, K., Lavik, E., Kiilgaard, J. F., Prause, J. U., Scherfig, E., Young, M., & la Cour, M. (2009). Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia. Experimental Eye Research, 89(6), 1012-20. https://doi.org/10.1016/j.exer.2009.08.014, https://doi.org/10.1016/j.exer.2009.08.014

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; Johansson, Ulrica Englund et al.

In: Experimental Eye Research, Vol. 89, No. 6, 01.12.2009, p. 1012-20.

Research output: Contribution to journal › Journal article › Research › peer-review

Kyhn, MV, Klassen, H, Johansson, UE, Warfvinge, K, Lavik, E, Kiilgaard, JF, Prause, JU, Scherfig, E, Young, M, la Cour, M, Kyhn, MV, Klassen, H, Johansson, UE, Warfvinge, K, Lavik, E, Kiilgaard, JF, Prause, JU, Scherfig, E, Young, M & la Cour, M 2009, 'Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia', Experimental Eye Research, vol. 89, no. 6, pp. 1012-20. https://doi.org/10.1016/j.exer.2009.08.014, https://doi.org/10.1016/j.exer.2009.08.014

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

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 < 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.",

author = "Kyhn, {Maria Voss} and Henry Klassen and Johansson, {Ulrica Englund} and Karin Warfvinge and Erin Lavik and Kiilgaard, {Jens F} and Prause, {Jan Ulrik} and Erik Scherfig and Michael Young and {la Cour}, Morten and Kyhn, {Maria Voss} and Henry Klassen and Johansson, {Ulrica Englund} and Karin Warfvinge and Erin Lavik and Kiilgaard, {Jens F} and Prause, {Jan Ulrik} and Erik Scherfig and Michael Young and {la Cour}, Morten",

note = "Keywords: Acute Disease; Animals; Cell Survival; Disease Models, Animal; Drug Administration Schedule; Drug Carriers; Drug Evaluation, Preclinical; Electroretinography; Female; Glial Cell Line-Derived Neurotrophic Factor; Ischemia; Microspheres; Neuroprotective Agents; Retinal Diseases; Retinal Ganglion Cells; Retinal Vessels; Sus scrofa",

year = "2009",

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day = "1",

doi = "10.1016/j.exer.2009.08.014",

language = "English",

volume = "89",

pages = "1012--20",

journal = "Experimental Eye Research",

issn = "0014-4835",

publisher = "Academic Press",

number = "6",

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T1 - Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia

AU - Kyhn, Maria Voss

AU - Klassen, Henry

AU - Johansson, Ulrica Englund

AU - Warfvinge, Karin

AU - Lavik, Erin

AU - Kiilgaard, Jens F

AU - Prause, Jan Ulrik

AU - Scherfig, Erik

AU - Young, Michael

AU - la Cour, Morten

AU - Kyhn, Maria Voss

AU - Klassen, Henry

AU - Johansson, Ulrica Englund

AU - Warfvinge, Karin

AU - Lavik, Erin

AU - Kiilgaard, Jens F

AU - Prause, Jan Ulrik

AU - Scherfig, Erik

AU - Young, Michael

AU - la Cour, Morten

N1 - Keywords: Acute Disease; Animals; Cell Survival; Disease Models, Animal; Drug Administration Schedule; Drug Carriers; Drug Evaluation, Preclinical; Electroretinography; Female; Glial Cell Line-Derived Neurotrophic Factor; Ischemia; Microspheres; Neuroprotective Agents; Retinal Diseases; Retinal Ganglion Cells; Retinal Vessels; Sus scrofa

PY - 2009/12/1

Y1 - 2009/12/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.exer.2009.08.014

DO - 10.1016/j.exer.2009.08.014

M3 - Journal article

C2 - 19735654

SN - 0014-4835

VL - 89

SP - 1012

EP - 1020

JO - Experimental Eye Research

JF - Experimental Eye Research

IS - 6

ER -

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

Abstract

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