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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.
- 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.
- The hemodynamic response function as a type 2 diabetes biomarker: a data-driven approachPublication . Guimarães, Pedro; Serranho, Pedro; Duarte, João V.; Crisóstomo, Joana; Moreno, Carolina; Gomes, Leonor; Bernardes, Rui; Castelo-Branco, MiguelIntroduction: There is a need to better understand the neurophysiological changes associated with early brain dysfunction in Type 2 diabetes mellitus (T2DM) before vascular or structural lesions. Our aim was to use a novel unbiased data-driven approach to detect and characterize hemodynamic response function (HRF) alterations in T2DM patients, focusing on their potential as biomarkers. Methods: We meshed task-based event-related (visual speed discrimination) functional magnetic resonance imaging with DL to show, from an unbiased perspective, that T2DM patients’ blood-oxygen-level dependent response is altered. Relevance analysis determined which brain regions were more important for discrimination. We combined explainability with deconvolution generalized linear model to provide a more accurate picture of the nature of the neural changes. Results: The proposed approach to discriminate T2DM patients achieved up to 95% accuracy. Higher performance was achieved at higher stimulus (speed) contrast, showing a direct relationship with stimulus properties, and in the hemispherically dominant left visual hemifield, demonstrating biological interpretability. Differences are explained by physiological asymmetries in cortical spatial processing (right hemisphere dominance) and larger neural signal-to-noise ratios related to stimulus contrast. Relevance analysis revealed the most important regions for discrimination, such as extrastriate visual cortex, parietal cortex, and insula. These are disease/task related, providing additional evidence for pathophysiological significance. Our data-driven design allowed us to compute the unbiased HRF without assumptions. Conclusion: We can accurately differentiate T2DM patients using a datadriven classification of the HRF. HRF differences hold promise as biomarkers and could contribute to a deeper understanding of neurophysiological changes associated with T2DM.
- When sex matters: differences in the central nervous system as imaged by OCT through the retinaPublication . Nunes, Ana; Serranho, Pedro; Guimarães, Pedro; Ferreira, João; Castelo-Branco, Miguel; Bernardes, RuiBackground: Retinal texture has gained momentum as a source of biomarkers of neurodegeneration, as it is sensitive to subtle differences in the central nervous system from texture analysis of the neuroretina. Sex differences in the retina structure, as detected by layer thickness measurements from optical coherence tomography (OCT) data, have been discussed in the literature. However, the effect of sex on retinal interocular differences in healthy adults has been overlooked and remains largely unreported. Methods: We computed mean value fundus images for the neuroretina layers as imaged by OCT of healthy individuals. Texture metrics were obtained from these images to assess whether women and men have the same retina texture characteristics in both eyes. Texture features were tested for group mean differences between the right and left eye. Results: Corrected texture differences exist only in the female group. Conclusions: This work illustrates that the differences between the right and left eyes manifest differently in females and males. This further supports the need for tight control and minute analysis in studies where interocular asymmetry may be used as a disease biomarker, and the potential of texture analysis applied to OCT imaging to spot differences in the retina.