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- Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's diseasePublication . Batista, Ana; Guimarães, Pedro; Martins, João; Moreira, Paula I.; Ambrósio, António F.; Castelo-Branco, Miguel; Serranho, Pedro; Bernardes, RuiAnimal models of disease are paramount to understand retinal development, the pathophysiology of eye diseases, and to study neurodegeneration using optical coherence tomography (OCT) data. In this study, we present a comprehensive normative database of retinal thickness in C57BL6/129S mice using spectral-domain OCT data. The database covers a longitudinal period of 16 months, from 1 to 16 months of age, and provides valuable insights into retinal development and changes over time. Our findings reveal that total retinal thickness decreases with age, while the thickness of individual retinal layers and layer aggregates changes in different ways. For example, the outer plexiform layer (OPL), photoreceptor inner segments (ILS), and retinal pigment epithelium (RPE) thickened over time, whereas other retinal layers and layer aggregates became thinner. Additionally, we compare the retinal thickness of wild-type (WT) mice with an animal model of Alzheimer's disease (3×Tg-AD) and show that the transgenic mice exhibit a decrease in total retinal thickness compared to age-matched WT mice, with statistically significant differences observed at all evaluated ages. This normative database of retinal thickness in mice will serve as a reference for future studies on retinal changes in neurodegenerative and eye diseases and will further our understanding of the pathophysiology of these conditions.
- Shedding light on early central nervous system changes for Alzheimer’s disease through the retina: an animal studyPublication . Bernardes, Rui; Ferreira, Hugo; Guimarães, Pedro; Serranho, PedroThe World Health Organization (WHO) 2015 projections estimated 75.6 million people living with dementia in 2030, an update from the 66 million estimated in 2013. These figures account for all types of dementia, but Alzheimer’s disease stands out as the most common estimated type, representing 60% to 80% of the cases. An increasing number of research groups adopted the approach of using the retina as a window to the brain. Besides being the visible part of the central nervous system, the retina is readily available through non-invasive imaging techniques such as optical coherence tomography (OCT). Moreover, cumulative evidence indicates that neurodegenerative diseases can also affect the retina. In the work reported herein, we imaged the retina of wild-type and the triple-transgenic mouse model of Alzheimer’s disease, at the ages of one-, two-, three-, four-, eight-, twelve- and sixteen-months-old, by OCT and segmented gathered data using a developed convolutional neural network into distinct layers. Group differences through texture analysis of computed fundus images for five layers of the retina, normative retinal thickness data throughout the observation period of the ageing mice, and findings related to the estimation of the ageing effect of the human genes present in the transgenic group, as well as the classification of individual fundus images through convolutional neural networks, will be presented and thoroughly discussed in the Special Session on ”New Developments in Imaging for Ocular and Neurodegenerative Disorders”.
- Retinal imaging in animal models: searching for biomarkers of neurodegenerationPublication . Batista, Ana; Guimarães, Pedro; Serranho, Pedro; Nunes, Ana; Martins, João; Moreira, Paula I.; Ambrósio, António F.; Morgado, Miguel; Castelo-Branco, Miguel; Bernardes, RuiThere is a pressing need for novel diagnostic and progression biomarkers of neurodegeneration. However, the inability to determine disease duration and stage in patients with Alzheimer’s disease (AD) hinders their discovery. Because animal models of disease allow us to circumvent some of these limitations, they have proven to be of paramount importance in clinical research. Due to the clear optics of the eye, the retina combined with optical coherence tomography (OCT) offers the perfect opportunity to image neurodegeneration in the retina in vivo, non-invasively, directly, quickly, and inexpensively. Based on these premises, our group has worked towards uncovering neurodegeneration-associated changes in the retina of the triple-transgenic mouse model of familial AD (3×Tg-AD). In this work, we present an overview of our work on this topic. We report on thickness variations of the retina and retinal layers/layer aggregates caused by healthy aging and AD-like conditions and discuss the implications of focusing research efforts solely on retinal thickness. We explore what other information is embedded in the OCT data, extracted based on texture analysis and deep-learning approaches, to further identify biomarkers that could be used for early detection and diagnosis. We were able to detect changes in the retina of the animal model of AD as early as 1 month of age. We also discuss our work to develop an optical coherence elastography system to measure retinal elasticity, which can be used in conjunction with conventional OCT. Finally, we discuss the potential application of these technologies in human patients and the steps needed to make OCT a helpful screening tool for the detection of neurodegeneration.