Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer’s Disease

Author:

Sánchez-Puebla Lidia123ORCID,de Hoz Rosa124ORCID,Salobrar-García Elena124ORCID,Arias-Vázquez Alberto1,González-Jiménez María1,Ramírez Ana I.124ORCID,Fernández-Albarral José A.124ORCID,Matamoros José A.14ORCID,Elvira-Hurtado Lorena1ORCID,Saido Takaomi C.5,Saito Takashi6ORCID,Nieto Vaquero Carmen789,Cuartero María I.8910,Moro María A.7ORCID,Salazar Juan J.124ORCID,López-Cuenca Inés124ORCID,Ramírez José M.123ORCID

Affiliation:

1. Ramon Castroviejo Institute for Ophthalmic Research, Complutense University of Madrid, 28040 Madrid, Spain

2. Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain

3. Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain

4. Department of Immunology, Ophthalmology and ENT, Faculty of Optics and Optometry, Complutense University of Madrid, 28040 Madrid, Spain

5. Brain Science Institute, RIKEN, Laboratory for Proteolytic Neuroscience, Wako 351-0198, Japan

6. Institute of Brain Science, Faculty of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan

7. Neurovascular Pathophysiology, Cardiovascular Risk Factor and Brain Function Programme, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain

8. Hospital 12 de Octubre Research Institute (i + 12), 28041 Madrid, Spain

9. University Institute for Research in Neurochemistry, Complutense University of Madrid (UCM), 28040 Madrid, Spain

10. Department of Pharmacology and Toxicology, Faculty of Medicine, Complutense University of Madrid (UCM), 28040 Madrid, Spain

Abstract

In Alzheimer’s disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans.

Funder

Spanish Ministry of Science and Innovation

Complutense University of Madrid

Publisher

MDPI AG

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