AI driven 3D subcellular RPE map discovers cell state transitions in establishment of apical-basal polarity

Published

January 12, 2026

Author(s)

Davide Ortolan, Pushkar Sathe, Andrei Volkov, Dominik Reichert, Sheldon Sebastian, Arvydas Maminishkis, Nicolas Schaub, Devika Bose, Jorge Alejandro Suarez de Freitas Ferrari, Nyusha Lin, Gianluca Pegoraro, Carl Simon, Ruchi Sharma, Peter Bajcsy, Kapil Bharti

Abstract

The retinal pigment epithelium (RPE) is a specialized cell monolayer that forms the barrier between the subretinal and choroidal spaces. During development, RPE cells polarize perpendicular to the monolayer plane such that organelles attain specific intracellular locations. This allows the RPE to differentially interact with overlying photoreceptors and underlying choriocapillaris. When RPE polarity is disrupted, tissue homeostasis is disturbed, leading to retinal degeneration. The subcellular organizational principles of RPE polarity are unknown. We developed an artificial intelligence (AI), specifically a mask region-based convolutional neural network-assisted high-content image analysis platform combined with mathematical modeling to develop a quantitative three-dimensional digital twin of RPE subcellular structures during the establishment of apical/basal polarity, polarity organization with learning-based analysis for RPE image segmentation (POLARIS). We discovered, during apical/basal polarization, cells constrict along the lateral axis and elongate apically, nuclear volume decreases, nuclear envelope develops invaginations, junctional complexes consolidate to the lateral membrane, the endoplasmic reticulum and mitochondria increase in volume and translocate towards the nucleus, and lysosomes move towards the central-apical side. AI algorithm and mathematical analysis reveal non-stochastic cell state transitions and organelle interactions in 3D during RPE polarization. These integrated AI-based quantitative data provide a reference digital twin to discover intracellular defects in diseased RPE..

Citation

npj Artificial Intelligence

Volume

2

Issue

20

Pub Type

Journals

Download Paper

https://doi.org/10.1038/s44387-026-00074-6

Local Download

Keywords

retinal pigment epithelium characterization, 3-dimensional maps of subcellular organelles, reference cell measurements

Citation

Ortolan, D. , Sathe, P. , Volkov, A. , Reichert, D. , Sebastian, S. , Maminishkis, A. , Schaub, N. , Bose, D. , Suarez de Freitas Ferrari, J. , Lin, N. , Pegoraro, G. , Simon, C. , Sharma, R. , Bajcsy, P. and Bharti, K. (2026), AI driven 3D subcellular RPE map discovers cell state transitions in establishment of apical-basal polarity, npj Artificial Intelligence, [online], https://doi.org/10.1038/s44387-026-00074-6, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=957950 (Accessed March 5, 2026)