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Imaging tools for automatic biomarkers analysis to evaluate progression in intermediate age-related macular degeneration
Publication . Lashkov, Vasilli; Matela, Nuno; Tenreiro, Sandra
Age-related macular degeneration (AMD) is a major cause of vision loss in elderly, with no effective treatments available. Ophthalmologists rely on retinal imaging, but manual comparison of features is time-consuming and subjective. We aimed to perform an automated longitudinal analysis of AMD biomarkers using previously developed by our group software. Here, advanced image processing and existing algorithms were used for quantifying drusen features at different timepoints, giving insights into disease progression and software’s limitations.
Optical Coherence Tomography (OCT) images were acquired using the SPECTRALIS platform (Heidelberg Engineering). The study utilized a total of 8 SD-OCT volumes obtained from 4 patients with intermediate AMD. Images quality was ensured by excluding scans with artifacts or those that could not be processed by the software. MATLAB was used for custom image analysis.
The results demonstrated an overall increase in drusen number and size over the follow-up period, consistent with known patterns of AMD progression. However, drusen volume changes were less consistent, possibly reflecting variability in disease mechanisms, patient-specific factors, or software limitations. Hyperreflective foci (HRF) were observed, but due to the small sample size, no clear patterns in their behavior over time could be established. The study's small sample size and variability in drusen dynamics limited the statistical analysis of the findings. Additionally, possible errors in automated segmentation could have contributed to these inconsistencies.
While the study identifies trends in drusen dynamics and their potential role in AMD progression, the limited sample size prevents drawing definitive conclusions, underscoring the need for further research. We also addressed the software’s limitations and proposed directions for future investigation. Follow-up studies should focus on larger sample sizes, incorporate a rigorous manual validation to capture the full range of drusen evolution, and expand the analysis to include other important AMD biomarkers, such as different phenotypes of OCT Reflective Drusen Substructures (ODS), hyporeflective central drusen, or structural changes in retinal pigment epithelium (RPE), external limiting membrane (ELM) and ellipsoid zone (EZ). With continued development and refinement, automated tools hold significant potential for advancing AMD research and improving disease monitoring.
Determining the role of a candidate peptide hormone ligand-receptor pair during pharate adult development in Drosophila
Publication . Varela, Ednilson Mascarenhas; Gontijo, Alisson; Homem, Catarina; Herédia, Fabiana
Insulin-like peptides (Ilps) of the Relaxin family have important functions in reproduction, development, and nervous system function across species and signal via Relaxin-specific G protein coupled receptors (GPCRs). In Drosophila, Ilp7 is the most highly conserved amongst the eight described Ilps, but its biological function remains unknown. The Drosophila Leucine-Rich Repeat-containing GPCR 4 (Lgr4) is a clear ortholog of the vertebrate Relaxin receptors, but which Drosophlia Ilp, if any, acts as its ligand, remains to be determined. Based on our evolutionary phylogenetic analysis I hypothesize that Ilp7 and Lgr4 form a ligand-receptor pair in Drosophila. Here, we incorporated GAL4 and LexA reporter genes in the endogenous Lgr4 locus (Lgr4::P2A::GAL4 or Lgr4::P2A::LexA, respectively) and used these reporters to infer Lgr4 expression patterns during Drosophila development. We find that most of the Lgr4-positive (Lgr4+) cells in the central nervous system (CNS) express the RNA-binding protein elav´ (embryonic lethal, abnormal vision), a postmitotic neuron marker, suggesting that most or all Lgr4+ cells are neurons, not glial or other cells in the CNS. By analyzing sequence data of our GAL4 and LexA alleles, we found out that there are two previously unnoticed Lgr4 alleles segregating in Drosophila stocks. Differences in Lgr4 expression patterns are observed between these alleles, particularly in the optic lobe. Neuroanatomical characterization identifies notable Lgr4+ cells in the pars intercerebralis (PI), distinct from insulin-producing cells (IPCs), suggesting functional significance. Lgr4 expression is also detected in the proventricular ganglion (PVG), ABLKs, and the gustatory systems, indicating extensive expression in both central and peripheral nervous systems with potential diverse functions. We show that mutants in either Ilp7 or Lgr4 do not exhibit obvious defects under normal laboratory conditions regarding development, fertility, and fecundity. However, both Ilp7 and Lgr4 mutants display aberrant light-avoidance behavior and play a crucial role at the end of late third-instar larvae, driving them to select a dark environment to pupariate. Moreover, we biochemically validated that Ilp7 and Lgr4 co-immunoprecipitate when epitope-tagged-versions of both proteins are ectopically co-expressed in cultured Drosophila S2 cells in vitro. Furthermore, we confirm that confinement induces a delay in D. melanogaster wing expansion using a different setup (our small chambers in the filming arenas), and we found that flies of the Ilp7 mutant stock (Ilp7[1]) fail to perform wing expansion behavior under confinement. Nevertheless, placing the Ilp7[1] mutation in another genetic background (RAL486) eliminated this effect.
Advancing Biotherapeutic Manufacturing Through New Purification Strategies
Publication . Fernandes, Rita Patrício; Peixoto, Cristina; Mota, José Paulo
"The bioprocessing of enveloped viral vectors and extracellular vesicles (EVs) has made significant advances in recent years, driven by their growing applications in gene therapy, vaccine development, and regenerative medicine. These biological entities, which include viral vectors such as lentiviruses, retroviruses, and oncolytic viruses, as well as therapeutic EVs, are essential for delivering genetic material and modulating intercellular communication. Their increasing relevance is reflected in the expanding number of clinical trials and therapeutic products leveraging these platforms. For instance, lentiviral vectors (LVs) have become critical tools in gene therapies targeting monogenic disorders and cell-based therapies, while extracellular vesicles are being explored for their potential in drug delivery and immune modulation. (...)"
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Programático
Número da atribuição
UIDP/04462/2020