RT Journal Article T1 Retinal Thickness Changes Over Time in a Murine AD Model APPNL-F/NL-F A1 García Martín, Elena Salobrar A1 López Cuenca, Inés A1 Sánchez Puebla, Lídia A1 Hoz Montañana, María Rosa de A1 Fernández Arrabal, José A. A1 Ramírez Sebastián, Ana Isabel A1 Bravo Ferrer, Isbel A1 Medina Alonso, Violeta A1 Moro Sánchez, María Ángeles A1 Saido, Takaomi C. A1 Saito, Takashi A1 Salazar Corral, Juan José A1 Ramirez Sebastian, Jose Manuel AB 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 APPNL−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 APPNL−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 APPNL−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 APPNL−F/NL−F AD model may help us better understand the different retinal changes during the progression of AD.Keywords: Alzheimer, retina, OCT, mouse model of AD, APPNL-F/NL-F PB Frontiers Media SN 1663-4365 YR 2021 FD 2021-01-15 LK https://hdl.handle.net/20.500.14352/7737 UL https://hdl.handle.net/20.500.14352/7737 LA eng NO Received: 03 November 2020; Accepted: 15 December 2020;Published: 15 January 2021. NO Instituto de Salud Carlos III NO Ministerio de Ciencia e Innovación (MICCIN) NO Leducq Fundation for Cardiovascular Research NO Universidad Complutense de Madrid DS Docta Complutense RD 8 may 2024