Dissecar os Biomarcadores de Neurodegeneração da Imagem do Fundo OCT: um Modelo Animal de Neuroinflamação Induzido por LPS

We aim for a future neurodegeneration screening using OCT. To accomplish this, early biomarkers are needed. We have already shown in humans the potential of our methodology (Nunes et al. 2019). However, in the real world, neurodegeneration can remain unsuspected for over 10 years before tentative diagnosis, losing a pivotal time window (Ritchie et al. 2016). Leveraging animal models of disease is the logical choice. Using the 3xTg-AD model, we revealed changes at the very beginning of these animals' lives (Ferreira et al. 2022). Widespread differences found throughout the retina highlight the potential of OCT for novel and improved early biomarkers. Despite these important results, because animals were already so different at the first acquisition (1 month old), our goal to detect neurodegeneration onset was not realized. The only way to control the onset of changes is with induced models. With this proposal we will leverage an LPS-Induced neuroinflammation model to control the onset of changes and investigate inflammation of the neuroretina, identify early biomarkers that are indicative of neurodegenerative processes, and bridge the gap between animal and human findings by investigating how OCT biomarkers relate to complex biochemical interactions. This proposal addresses several critical challenges in the field of NDs, leveraging innovative approaches. EARLY DETECTION OF NEURODEGENERATION: Early detection remains a significant hurdle. The project proposes using OCT to identify biomarkers of neurodegeneration in the retina, potentially before clinical symptoms manifest. Our approach could substantially advance early detection capabilities, as the eye offers a unique, accessible window to the CNS. UNTANGLING NEUROINFLAMMATION: Neuroinflammation is a critical factor in the pathogenesis of neurodegeneration. By inducing neuroinflammation and monitoring the onset and progression of inflammation in the neuroretina via OCT imaging and biochemical analysis, the project seeks to elucidate the mechanisms by which it contributes to neurodegenerative processes. COST-EFFECTIVE DIAGNOSTIC TOOLS: Current NDs diagnostics often involve expensive and inaccessible neuroimaging techniques. OCT offers a non-invasive, inexpensive, and widely available alternative. The project's focus on developing OCT as a diagnostic tool addresses the need for more accessible diagnostics, which is particularly important for early detection and monitoring disease progression. BIOMARKER SPECIFICITY AND SENSITIVITY: Retinal thinning is the most investigated OCT biomarker of NDs (Byun et al. 2021). It is an important indicative of OCT potential. However, thickness-based analysis alone raises important concerns: 1) It is error prone; 2) Suffers from low specificity; 3) It abdicates the possibility of earlier diagnosis; 4) It forgoes a wealth of information embedded in the signal. Our methodology goes beyond traditional methods by exploring signal statistics, texture analysis, and machine learning. MULTIDISCIPLINARY APPROACH: The complexity of neurodegeneration needs a multidisciplinary approach, integrating insights from neurology, imaging, and molecular biology. This proposal embodies this approach by combining advanced imaging, data science, and biochemistry for a deeper understanding of neurodegeneration, identifying biomarkers, and enhancing research translation.