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Palkova, M.

Publications and source records attributed to Palkova, M..

2 recordsLinked to original sources

Automated Retinal Dysplasia Segmentation in Mouse Optical Coherence Tomography Scans Using a UNet-Based model

PurposeOptical coherence tomography (OCT) is the state-of-the-art non-invasive imaging technique for preclinical retinopathy studies. However, manual pathology annotations in mouse OCT scans are labour-intensive and susceptible to inter-rater variability. To alleviate these issues, we developed a neural network-based model for automated annotation of retinal dysplasia in mouse OCT scans. MethodsOur model was trained on 205 expert-annotated OCT stacks and validated on 40 unseen stacks with additional expert annotation comparisons in a subset of them. ResultsThe model detects pathologies with high accuracy (F1-score > 0.95) and consistency with experts (median Dice score > 0.8). We integrated the model into a cross-platform app ("OCTOPUS") that includes batch processing, automated annotation, manual annotation editing, and quantitative longitudinal tracking with pathological area estimation on the fundus image, and exportable results in CSV and SVG formats. ConclusionsOur open-source tool aims to facilitate and standardise OCT assessments between laboratories for efficient preclinical screening and high-throughput phenotyping in mouse models of retinal disease.

bioinformatics↗

Retinitis pigmentosa associated mutations in mouse Prpf8 cause misexpression of circRNAs and degeneration of cerebellar granule neurons

A subset of patients suffering from a familial retinitis pigmentosa (RP) carry mutations in several spliceosomal components including PRPF8 protein. Here, we established two novel alleles of murine Prpf8 that genocopy or mimic aberrant PRPF8 found in RP patients - the substitution p.Tyr2334Asn and an extended protein variant p.Glu2331ValfsX15. Homozygous mice expressing either of the aberrant Prpf8 variants developed within first 2 months progressive atrophy of the cerebellum due to extensive granule neuron loss. Comparison of transcriptome from pre-degenerative and degenerative tissues revealed a subset of circRNAs that were deregulated in all tissues and both Prpf8-RP mouse strains. To identify potential risk factors that sensitize cerebellum for Prpf8 mutations we monitored expression of several splicing proteins during first eight weeks. We observed downregulation of all selected splicing proteins in wild-type cerebellum, which coincided with neurodegeneration onset. The decrease in splicing protein expression was further pronounced in mouse strains expressing mutated Prpf8. Collectively, we propose a model where physiological reduction of spliceosomal components during postnatal tissue maturation sensitizes cells to expression of aberrant Prpf8 and the subsequent deregulation of circRNAs triggers neuron death.

neuroscience↗