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.
authors.affiliation: Department of Ophthalmology, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Maria Voss
authors.initials: MV
authors.lastname: Kyhn
authors.forename: Henry
authors.initials: H
authors.lastname: Klassen
authors.forename: Ulrica Englund
authors.initials: UE
authors.lastname: Johansson
authors.forename: Karin
authors.initials: K
authors.lastname: Warfvinge
authors.forename: Erin
authors.initials: E
authors.lastname: Lavik
authors.forename: Jens F
authors.initials: JF
authors.lastname: Kiilgaard
authors.forename: Jan Ulrik
authors.initials: JU
authors.lastname: Prause
authors.forename: Erik
authors.initials: E
authors.lastname: Scherfig
authors.forename: Michael
authors.initials: M
authors.lastname: Young
authors.forename: Morten
authors.initials: M
authors.lastname: la Cour
mesh_terms: D000208:Acute Disease; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004596:Electroretinography / Q000187:drug effects; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D007511:Ischemia / Q000473:pathology / Q000517:prevention & control*; D008863:Microspheres; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D012164:Retinal Diseases / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology*; D034421:Sus scrofa
chemical_list: D004337:Drug Carriers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents