Distribution of amyloid precursor protein and amyloid-beta in ocular hypertensive C57BL/6 mouse eyes.
OBJECTIVE
Amyloid precursor protein (APP) and amyloid-beta (Abeta) appear to participate in the pathophysiology of retinal ganglion cell (RGC) death in glaucoma. We, therefore, determined the distribution of APP and Abeta in the retinas of C57BL/6 mice after induction of chronic ocular hypertension.


METHODS
Ocular hypertension was induced in one eye of three-month-old C57BL/6 mice by injection of hypertonic saline into episcleral veins. After 6 weeks of documented elevated intraocular pressure (IOP), retinas were fixed with 4% paraformaldehyde and processed for immunohistochemistry with antibodies including a polyclonal antibody to the C-terminus of Abeta 40 (Novartis 17-40/23) and a polyclonal antibody to the APP ectodomain (Novartis 474). Distribution and semiquantitative expression of APP and Abeta immunolabeling in ocular hypertensive and control retinas were graded in a masked fashion and compared.


RESULTS
APP and Abeta immunoreactivity was found in the pia/dura, optic nerve (ON), and RGC layer of ocular hypertensive retinas, whereas APP and Abeta immunoreactivity in the contralateral control eyes was detected only in the pia/dura. Comparison of ocular hypertensive and control eyes for Abeta immunolabeling was significant in the ON and RGC layer (p < 0.05) whereas no significant difference was found when compared for APP staining.


CONCLUSIONS
High Abeta and APP levels were seen in ocular hypertensive retinas, probably due to abnormal APP-splicing in the presence of elevated IOP.
Kipfer-Kauer
Anna
A
Department of Ophthalmology, University of Bern, Bern, Switzerland.
McKinnon
Stuart J
SJ
Frueh
Beatrice E
BE
Goldblum
David
D
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004388:Dura Mater / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007429:Intraocular Pressure; D051379:Mice; D008810:Mice, Inbred C57BL; D009798:Ocular Hypertension / Q000378:metabolism*; D009900:Optic Nerve / Q000378:metabolism*; D010841:Pia Mater / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D014065:Tonometry, Ocular
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor
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