Hotaling, N. | Search bioRxiv

bioRxiv2026

muDM: A Queryable Multi-Resolution Data Model for Vector Geometry in Spatial Bioimaging

Spatial bioimaging combines raster imagery with vector geometries that encode molecular measurements, connectivity, and anatomical labels. A major challenge is to connect and jointly query these resources at scale, because the vector structures that locate them cannot be searched across resolutions. muDM is a spatial data model for associating vector geometry with its annotated records. Under a single schema, it arranges 2D and 3D geometries, together with their identities and measurements, as a precomputed multi-resolution pyramid, a columnar store that can be queried in place from object storage and equivalent render-ready tiles from the same index. Deployed in a public catalog containing more than 100 datasets, this single model supports connectome meshes, multiplexed tissue imaging, and spatial transcriptomics. For neuron meshes, classifiers which use geometry together with linked synapse counts exceed the performance of geometry-only models, while coarser levels preserved most balanced accuracy and using up to two orders of magnitude less stored geometry.

bioinformatics↗

bioRxiv2019

Choroid-resident macrophages maintain local vasculature and RPE integrity and spontaneously regenerate following depletion

The choroid of the eye provides necessary vascular supply to the outer retina across the retinal pigment epithelial (RPE) layer and is a locus of progressive degenerative change in aging and age-related macular degeneration (AMD). Cellular mechanisms that maintain or compromise choroidal vasculature homeostasis are not well understood, complicating therapeutic efforts. We discover here that pharmacological ablation of macrophages normally resident in the adult mouse choroid via blockade of the CSF1 receptor resulted in progressive thinning of the choroid layer and atrophy of the choriocapillaris. Concurrently, choroidal macrophage ablation also induced structural disorganization of the RPE cell layer, downregulation of RPE visual cycle genes, and altered RPE angiogenic factor expression. Suspension of CSF1R blockade following ablation conversely enabled spontaneous regeneration of the choroidal macrophage population, restoring original macrophage distribution and morphological features. Macrophage repopulation significantly ameliorated the ablation-induced changes in RPE structure and angiogenic factor expression and arrested choroidal vascular atrophy. These findings reveal a previously unsuspected trophic function of resident choroidal macrophages in the maintenance of choroidal vasculature and the RPE layer, suggesting that insufficiency of macrophage function may contribute to age- and AMD-associated pathology. Modulating choroidal macrophage support function can constitute a strategy for therapeutic preservation of the choroid and RPE in AMD prevention and treatment. Significance StatementChoroidal atrophy is associated with normal aging and progression in age-related macular degeneration (AMD), a leading cause of blindness. Herein, we identify the choroidal macrophage as a critical player in the homeostatic maintenance of choroid-RPE complex of the eye. Depletion of choroidal macrophages resulted in progressive vascular atrophy, altered structure of retinal pigment epithelial (RPE) cells, and dysregulated RPE expression of visual cycle protein and angiogenic factors, VEGF and PEDF. We discovered that choroidal macrophages can regenerate and repopulate the choroid following depletion, ameliorating RPE alterations and arresting vascular atrophy. Our results suggest that insufficiency of macrophage function may contribute to age- and AMD-associated pathology, and modulation of macrophage support functions may be therapeutically useful in AMD prevention and treatment.

immunology↗