The c-jun N-terminal kinase plays a key role in ocular degenerative changes in a mouse model of alzheimer disease suggesting a correlation between ocular and brain pathologies

Lucia Buccarello, Alessandra Sclip, Matteo Sacchi, Anna Maria Castaldo, Ilaria Bertani, Andrea ReCecconi, Silvia Maestroni, Gianpaolo Zerbini, Paolo Nucci, Tiziana Borsello

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Recently a range of ocular manifestations such as retinal and lens amyloidbeta accumulation and retinal nerve fiber layer loss have been proposed as potential biomarkers in Alzheimer disease (AD). The TgCRND8 mouse model of AD exhibits age-dependent amyloid β (Aβ) oligomers accumulation and cognitive defects, amyloid plaques and hyperphosphorylated Tau deposition and inflammation. We proved the correlation between ocular pathologies and AD, observing increased levels of p-APP and p-Tau, accumulation of Aβ oligomers in the retina, eye, and optic nerve. The accumulation of amyloid markers was significantly stronger in the retinal ganglion cell (RGC) layer, suggesting that RGC might be more susceptible to degeneration. We detected a thinning of the RGC layer as well as RGC death in the retina of TgCRND8 mice, by using a combination of Optical Coherence Tomography (OCT), immunofluorescence, immunohistochemistry and Western blotting techniques. We proved for the first time the key role of C-Jun N-terminal Kinase (JNK) in the ocular degeneration. In support of this, the administration of the JNK inhibitor, D-JNKI1, was able to counteract the Aβ and p-Tau accumulation in the retina of TgCRND8 mice, and consequently reduce RGCs loss. These results confirm that degenerative changes in the retina/eye of AD mouse model mirrors the events observed in the brain parenchyma. Ocular changes can be detected by non-invasive imaging techniques, such as OCT, to study and test different therapeutic strategies against degenerative events associated to AD.

Original languageEnglish
Pages (from-to)83038-83051
Number of pages14
JournalOncotarget
Volume8
Issue number47
DOIs
Publication statusPublished - Jan 1 2017

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JNK Mitogen-Activated Protein Kinases
Retinal Ganglion Cells
Alzheimer Disease
Retina
Pathology
Brain
Eye Diseases
Optical Coherence Tomography
Amyloid
Eye Manifestations
Phosphotransferases
Amyloid Plaques
Optic Nerve
Nerve Fibers
Lenses
Fluorescent Antibody Technique
Cell Death
Biomarkers
Western Blotting
Immunohistochemistry

Keywords

  • Alzheimer's disease
  • JNK
  • Optical coherence tomography
  • Retinal ganglion cell layer
  • Stress signaling pathway

ASJC Scopus subject areas

  • Oncology

Cite this

The c-jun N-terminal kinase plays a key role in ocular degenerative changes in a mouse model of alzheimer disease suggesting a correlation between ocular and brain pathologies. / Buccarello, Lucia; Sclip, Alessandra; Sacchi, Matteo; Castaldo, Anna Maria; Bertani, Ilaria; ReCecconi, Andrea; Maestroni, Silvia; Zerbini, Gianpaolo; Nucci, Paolo; Borsello, Tiziana.

In: Oncotarget, Vol. 8, No. 47, 01.01.2017, p. 83038-83051.

Research output: Contribution to journalArticle

Buccarello, Lucia ; Sclip, Alessandra ; Sacchi, Matteo ; Castaldo, Anna Maria ; Bertani, Ilaria ; ReCecconi, Andrea ; Maestroni, Silvia ; Zerbini, Gianpaolo ; Nucci, Paolo ; Borsello, Tiziana. / The c-jun N-terminal kinase plays a key role in ocular degenerative changes in a mouse model of alzheimer disease suggesting a correlation between ocular and brain pathologies. In: Oncotarget. 2017 ; Vol. 8, No. 47. pp. 83038-83051.
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