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.

KEYWORDS::

• Alzheimer
• Amyloid
• Amyloid precursor protein
• Glaucoma
• Optic nerve

ACKNOWLEDGMENTS

The authors thank Mathias Jucker, M.D. (Neuropathology, Hertie-Institut für klinische Hirnforschung, Tuebingen, Germany) and Mathias Staufenbiel, M.D. (Novartis, Basel, Switzerland) for generously providing brain tissue of APP23 transgenic mice and Paolo Paganetti, M.D. (Novartis, Basel, Switzerland) for the kind supply of the primary antibodies. Furthermore, we thank Lorraine Kasmala, Anezka Chrenkowa, and Aniela Olac for expert technical and research assistance.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.