AI Article Synopsis

  • The study investigates the role of amyloid precursor protein (APP) and amyloid-beta (Abeta) in the death of retinal ganglion cells in glaucoma, focusing on their distribution in C57BL/6 mice.
  • After inducing chronic ocular hypertension in the mice, immunohistochemistry was used to analyze the levels of APP and Abeta in the retinas, revealing significant differences between hypertensive and control eyes.
  • The findings indicate that elevated intraocular pressure likely causes abnormal processing of APP, leading to increased levels of both APP and Abeta in the retinas affected by glaucoma.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697739PMC
http://dx.doi.org/10.3109/02713683.2010.494240DOI Listing

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