Retinal Thickness Changes Over Time in a Murine AD Model APP NL-F/NL-F

Elena Salobrar-García; Inés López-Cuenca; Lídia Sánchez-Puebla; Rosa de Hoz; José A Fernández-Albarral; Ana I Ramírez; Isabel Bravo-Ferrer; Violeta Medina; María A Moro; Takaomi C Saido; Takashi Saito; Juan J Salazar; José M Ramírez

doi:10.3389/fnagi.2020.625642

Retinal Thickness Changes Over Time in a Murine AD Model APP ^NL-F/NL-F

Front Aging Neurosci. 2021 Jan 15:12:625642. doi: 10.3389/fnagi.2020.625642. eCollection 2020.

Authors

Elena Salobrar-García^{1

2}, Inés López-Cuenca¹, Lídia Sánchez-Puebla¹, Rosa de Hoz^{1

2}, José A Fernández-Albarral¹, Ana I Ramírez^{1

2}, Isabel Bravo-Ferrer^{3

4}, Violeta Medina⁵, María A Moro⁵, Takaomi C Saido⁶, Takashi Saito⁷, Juan J Salazar^{1

2}, José M Ramírez^{1

8}

Affiliations

¹ Ramon Castroviejo Ophthalmological Research Institute, Complutense University of Madrid, Madrid, Spain.
² Department of Immunology, Ophthalmology and Ear, Nose, and Throat, Faculty of Optics and Optometry, Complutense University of Madrid, Madrid, Spain.
³ Department of Pharmacology and Toxicology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
⁴ Edinburgh Medical School, UK Dementia Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
⁵ Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
⁶ Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, Wako, Japan.
⁷ Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
⁸ Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, Madrid, Spain.

Abstract

Background: Alzheimer's disease (AD) may present retinal changes before brain pathology, suggesting the retina as an accessible biomarker of AD. The present work is a diachronic study using spectral domain optical coherence tomography (SD-OCT) to determine the total retinal thickness and retinal nerve fiber layer (RNFL) thickness in an APP^NL-F/NL-F mouse model of AD at 6, 9, 12, 15, 17, and 20 months old compared to wild type (WT) animals. Methods: Total retinal thickness and RNFL thickness were determined. The mean total retinal thickness was analyzed following the Early Treatment Diabetic Retinopathy Study sectors. RNFL was measured in six sectors of axonal ring scans around the optic nerve. Results: In the APP^NL-F/NL-F group compared to WT animals, the total retinal thickness changes observed were the following: (i) At 6-months-old, a significant thinning in the outer temporal sector was observed; (ii) at 15-months-old a significant thinning in the inner temporal and in the inner and outer inferior retinal sectors was noticed; (iii) at 17-months-old, a significant thickening in the inferior and nasal sectors was found in both inner and outer rings; and (iv) at 20-months-old, a significant thinning in the inner ring of nasal, temporal, and inferior retina and in the outer ring of superior and temporal retina was seen. In RNFL thickness, there was significant thinning in the global analysis and in nasal and inner-temporal sectors at 6 months old. Thinning was also found in the supero-temporal and nasal sectors and global value at 20 months old. Conclusions: In the APP^NL-F/NL-F AD model, the retinal thickness showed thinning, possibly produced by neurodegeneration alternating with thickening caused by deposits and neuroinflammation in some areas of the retina. These changes over time are similar to those observed in the human retina and could be a biomarker for AD. The APP^NL-F/NL-F AD model may help us better understand the different retinal changes during the progression of AD.

Keywords: APPNL-F/NL-F; Alzheimer; OCT; mouse model of AD; retina.