Distribution of amyloid precursor protein and amyloid-beta in ocular hypertensive C57BL/6 mouse eyes.
PURPOSE: 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.
Duke Scholars
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Related Subject Headings
- Tonometry, Ocular
- Retinal Ganglion Cells
- Retina
- Pia Mater
- Optic Nerve
- Ophthalmology & Optometry
- Ocular Hypertension
- Mice, Inbred C57BL
- Mice
- Intraocular Pressure
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tonometry, Ocular
- Retinal Ganglion Cells
- Retina
- Pia Mater
- Optic Nerve
- Ophthalmology & Optometry
- Ocular Hypertension
- Mice, Inbred C57BL
- Mice
- Intraocular Pressure