Distribution of Amyloid Precursor Protein and Amyloid-β in Ocular Hypertensive C57BL/6 Mouse Eyes

Abstract

Purpose: Amyloid precursor protein (APP) and amyloid-beta (Aβ) appear to participate in the pathophysiology of retinal ganglion cell (RGC) death in glaucoma. We, therefore, determined the distribution of APP and Aβ 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 Aβ 40 (Novartis 17-40/23) and a polyclonal antibody to the APP ectodomain (Novartis 474). Distribution and semiquantitative expression of APP and Aβ immunolabeling in ocular hypertensive and control retinas were graded in a masked fashion and compared.Results: APP and Aβ immunoreactivity was found in the pia/dura, optic nerve (ON), and RGC layer of ocular hypertensive retinas, whereas APP and Aβ immunoreactivity in the contralateral control eyes was detected only in the pia/dura. Comparison of ocular hypertensive and control eyes for Aβ 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 Aβ and APP levels were seen in ocular hypertensive retinas, probably due to abnormal APP-splicing in the presence of elevated IOP.