Biology subjects

Maes, M. E.

Publications and source records attributed to Maes, M. E..

5 recordsLinked to original sources

bioRxiv2026

Chromatic topological mapping reveals organelle-specific spatial organization within microglia

In branched cells, including neurons and glia, intracellular organelles are distributed across complex cellular arbors where their spatial arrangement supports transport, signaling, and compartmentalized function. Although intracellular organelle organization is increasingly recognized as an important feature of cellular state and function, existing approaches assess organelle abundance or spatial position without accounting for the branching architecture that shapes cellular function. Here, we introduce the chromatic topological morphology descriptor (chromatic TMD), a framework that quantitatively resolves intracellular organization in relation to branching morphology. Applied to reconstructed microglia with annotated lysosomal and mitochondrial compartments across retinal layers and after optic nerve crush injury, chromatic TMD identifies distinct organelle-specific spatial programs: CD68+-endosomal-lysosomes undergo layer-dependent branch-specific redistribution, revealing selective intracellular reorganization after injury, whereas mitochondrial organization remains closely coupled to branching morphology. These findings establish intracellular organization as an additional layer of cellular architecture that can be systematically analyzed across branched neural cells.

neuroscience↗

bioRxiv2024

Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye.

PurposeOptic nerve crush (ONC) is a model for studying optic nerve trauma. Unilateral ONC induces massive retinal ganglion cell (RGC) degeneration in the affected eye, leading to vision loss within a month. A common assumption has been that the non-injured contralateral eye is unaffected due to the minimal anatomical decussation of the RGC projections at the chiasm. Yet, recently, microglia, the brain-resident macrophages, have shown a responsive phenotype in the contralateral eye after ONC. Whether RGC loss accompanies this phenotype is still controversial. MethodsUsing the available RGCode algorithm and developing our own RGC-Quant deep-learning-based tool, we quantify RGCs total number and density across the entire retina after ONC. ResultsWe confirm a short-term microglia response in the contralateral eye after ONC, but this did not affect microglia number. Furthermore, we cannot confirm the previously reported RGC loss between naive and contralateral retinas five weeks after ONC induction across the commonly used Cx3cr1creERT2 and C57BL6/J mouse models. Neither sex nor the direct comparison of the RGC markers Brn3a and RBPMS, with Brn3a co-labeling, on average, 89% of the RBPMS+-cells, explained this discrepancy, suggesting that the early microglia-responsive phenotype does not have immediate consequences on the RGC number. ConclusionsOur results corroborate that unilateral optic nerve injury elicits a microglial response in the uninjured contralateral eye but without RGC loss. Therefore, the contralateral eye should be treated separately and not as an ONC control.

neuroscience↗

bioRxiv2022

Sex, stress and UCP2: mitochondria illuminate microglial identity beyond the dichotomy

Balanced and dynamic mitochondrial networks are essential for cell survival and function. Mitochondrial networks remodel their connectivity, content and subcellular localization to support optimized energy production under conditions of increased stress. In vivo, stressors can arise from the environment, such as in neuronal injury, or from mutation-induced cellular dysfunction. Cells programmed to identify and respond to these stress signals, like microglia, rely on optimized mitochondrial function, however we know very little about mitochondrial networks of microglia in vivo or their adaptation to environmental or cellular stressors. Here, we define the mitochondrial networks of retinal microglia in physiological conditions in vivo and evaluate network alterations by taking advantage of a microglia-selective mitochondria-labeled mouse model. First, we demonstrate significant differences in the mitochondrial networks of microglia in vivo and in vitro. Then, we induced neuronal injury in the in vivo environment using optic nerve crush, where responsive microglia exhibit more fragmented mitochondrial networks with increased content and perinuclear localization, supporting a state of increased cellular stress. Surprisingly, when we selectively increase cellular stress by knocking out the mitochondria-associated gene uncoupling protein 2 (UCP2), only male UCP2KO microglia establish a hyperfused mitochondrial network after injury, indicating sex differences in microglial stress mitigation. Ovariectomy in UCP2KO females elicits a shift toward the male hyperfused mitochondrial phenotype suggesting that circulating estrogens are a contributing factor to the differences in microglial stress mitigation.

neuroscience↗

bioRxiv2021

Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment

Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy likely due to the cells heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette.Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.

neuroscience↗

bioRxiv2020

Extending and repeating assessments is a key tool to reveal barriers to effective management of protected areas

Here we assessed protected area (PA) management effectiveness while also checking for potential barriers. We addressed 21 PAs of the State of Santa Catarina, southern Brazil. Out of these, we assessed 10 PAs under state level administration that lacked thus far a standardized assessment. For PAs under federal administration, we got assessment data from the government itself. We contrasted the PAs regarding the level of administration and collected a list of aspects that could result in differences in management effectiveness between PAs. We checked the relationship between PA aspects and mean effectiveness with linear models. The same aspects were also related to PA management elements, namely context, planning, inputs, processes, and outputs, using redundancy analysis. Management effectiveness and scores of management elements were found to be lower for PAs either with unresolved land tenure, lacking management plans, being under many pressures and threats, or being under state level administration. Our results call for extended assessments to reach the reality of the Brazilian PA network with different administration levels. Assessments must be carried out regularly since it is the only way to effectively flag a barrier, clear it, then find the next one to be tackled.

ecology↗