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

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.

From Alzheimer's disease to vascular dementia: Different roads leading to cognitive decline.

LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Retinal Vascular and Structural Changes in the Murine Alzheimer's APPNL-F/NL-F Model from 6 to 20 Months.

Alzheimer's disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models.

Aumento de expresión y actividad de MMP-9 en rinosinusitis crónica con poliposis nasal / Increased expression and activity of MMP-9 in chronic rhinosinusitis with nasal polyposis

Introducción: Las metaloproteinasas de matriz (MMP) son un conjunto de endopeptidasas implicadas en la degradación de la matriz extracelular, que podrían explicar los cambios histológicos característicos de la poliposis nasal. El objetivo de este estudio consiste en determinar la implicación de MMP-2 y MMP-9 en la rinosinusitis crónica con poliposisnasal. Material y método: Para ello, se tomaron muestras de 15 pacientes afectados de poliposis nasal y muestras de 15 controles intervenidos de turbinoplastia. Las muestras se procesaron para análisis de la expresión de ambas MMP mediante Western blot, y para determinación de su actividad enzimática mediante cimografía. Resultados: Los resultados mostraron un incremento de la actividad y de la expresión de MMP-9, pero no de MMP-2,en las muestras procedentes de pacientes afectados de poliposis nasal en comparación con los controles. Conclusiones: Estos resultados apoyarían la implicación de la MMP-9 en la remodelación tisular característica de esta enfermedad (AU)

Introduction: Matrix metalloproteinases (MMP) are a family of endopeptidases involved in extracellular matrix degradation and which could potentially explain specific histological changes in nasal polyposis. The aim of this study is to determine whether MMP-2 and 9 are involved in chronic rhinosinusitis with polyposis. Material and method: Specimens were collected from 15 patients affected by nasal polyposis and 15 control patients(with turbinoplasty performed). Specimens were processed for determination of protein expression levels by Western-blot and for determination of their enzymatic activity by zymography for both MMPs. Results: Results showed a higher expression and activity of MMP-9 but not of MMP-2 in specimens from patients with polyposis when compared with controls. Conclusions: These results support the involvement ofMMP-9 in the tissue remodelling characteristic of this disease (AU)