title: Lack of neuroprotection against experimental glaucoma in c-Jun N-terminal kinase 3 knockout mice.
abstract: To determine if the absence of c-Jun N-terminal kinase 3 (JNK3) in the mouse retina would reduce retinal ganglion cell (RGC) loss in mice with experimental glaucoma. C57BL/6 mice underwent experimental intraocular pressure (IOP) elevation with a bead/viscoelastic injection into one eye. One-half of the mice were Jnk3 homozygous knockouts (KO) and were compared to wild type (WT) mice. IOP was measured under anesthesia with the TonoLab, axial length was measured post-mortem with calipers after inflation to 15mmHg, and RGC layer counts were performed on retinal whole mount images stained with DAPI, imaged by confocal microscopy, and counted by masked observers in an image analysis system. Axon counts were performed in optic nerve cross-sections by semi-automated image analysis. Both WT and Jnk3(-/-) mice had mean elevations of IOP of more than 50% after bead injection. Both groups underwent the expected axial globe elongation due to chronic IOP elevation. The absence of JNK3 in KO retina was demonstrated by Western blots. RGC layer neuron counts showed modest loss in both WT and Jnk3(-/-) animals; local differences by retinal eccentricity were detected, in each case indicating greater loss in KO animals than in WT. The baseline number of RGC layer cells in KO animals was 10% higher than in WT, but the number of optic nerve axons was identical in KO and WT controls. A slightly greater loss of RGC in Jnk3(-/-) mice compared to controls was detected in experimental mouse glaucoma by RGC layer counting and there was no protective effect shown in axon counts. Counts of RGC layer cells and optic nerve axons indicate that Jnk3(-/-) mice have an increased number of amacrine cells compared to WT controls.
authors.affiliation: Glaucoma Research Laboratory, Wilmer Eye Institute, 600 North Wolfe Street, Johns Hopkins University School of Medicine, Baltimore, MD 21287-9205, USA. hquigley@jhmi.edu
authors.forename: Harry A
authors.initials: HA
authors.lastname: Quigley
authors.forename: Frances E
authors.initials: FE
authors.lastname: Cone
authors.forename: Scott E
authors.initials: SE
authors.lastname: Gelman
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.forename: Janice L
authors.initials: JL
authors.lastname: Son
authors.forename: Ericka N
authors.initials: EN
authors.lastname: Oglesby
authors.forename: Mary E
authors.initials: ME
authors.lastname: Pease
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
mesh_terms: D025042:Amacrine Cells / Q000473:pathology; D000818:Animals; D058452:Axial Length, Eye; D001369:Axons / Q000473:pathology*; D015153:Blotting, Western; D002452:Cell Count; D019610:Cytoprotection; D004195:Disease Models, Animal; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D007429:Intraocular Pressure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D048057:Mitogen-Activated Protein Kinase 10 / Q000502:physiology*; D009798:Ocular Hypertension / Q000473:pathology; D009901:Optic Nerve Diseases / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000473:pathology*; D051843:Synucleins / Q000378:metabolism; D014065:Tonometry, Ocular
chemical_list: D051843:Synucleins; D048057:Mitogen-Activated Protein Kinase 10