The “in silico–in vitro–in vivo” funnel holds significant potential for identifying targets to control cellular processes in research and clinical applications. In this report, we describe a framework for identifying, selecting, and applying chemokines to direct retinal neuron migration in vivo within the adult mouse retina.
Controlling donor and newborn neuron migration and maturation in the eye through microenvironment engineering
Jonathan R. Soucy, Levi Todd, Emil Kriukov, Monichan Phay, Volha V. Malechka, John Dayron Rivera, Thomas A. Reh, Petr Baranov | PNAS | 2023
Johnson TV, Calkins DJ, Fortune B, Goldberg JL, La Torre A, Lamba DA, Meyer JS, Reh TA, Wallace VA, Zack DJ, Baranov P. | iScience | 2023
The importance of unambiguous cell origin determination in neuronal repopulation studies
Using the retina as an example, we discuss common reasons for artifactual labeling of endogenous host neurons with donor cell reporters and suggest strategies to prevent erroneous conclusions based on misidentification of cell origin.
Soucy JR et al. | Mol Neurodegeneration | 2023
Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium
The RReSTORe Consortium outlines a comprehensive roadmap for retinal ganglion cell (RGC) repopulation to restore vision lost due to optic neuropathies. They identify five critical areas: RGC development and differentiation, transplantation methods and models, RGC survival and maturation, inner retinal wiring, and eye-to-brain connectivity. By addressing these challenges through multidisciplinary approaches, the consortium aims to advance therapeutic strategies for vision restoration.
J. Oswald, E. Kegeles, T. Minelli, P. Volchkov, P. Baranov | Mol Ther Methods Clin Dev. | 2021
Transplantation of miPSC/mESC-derived retinal ganglion cells into healthy and glaucomatous retinas
Optic neuropathies, including glaucoma, are a group of neurodegenerative diseases, characterized by the progressive loss of retinal ganglion cells (RGCs), leading to irreversible vision loss. While previous studies demonstrated the potential to replace RGCs with primary neurons from developing mouse retinas, their use is limited clinically.
E. Kegeles, A. Naumov, E. Karpulevich, P. Volchkov, P. Baranov | Front Neurosci. | 2020
Convolutional Neural Networks Can Predict Retinal Differentiation in Retinal Organoids
We have developed a deep learning-based computer algorithm to recognize and predict retinal differentiation in stem cell-derived organoids based on bright-field imaging. The three-dimensional "organoid" approach for the differentiation of pluripotent stem cells (PSC) into retinal and other neural tissues has become a major in vitro strategy to recapitulate development.
Using scRNAseq, we assembled a comprehensive atlas of human fetal retina development from week 8 to week 27, focusing on retinal ganglion cells (RGC). By applying pseudotime analysis, we mapped continuous RGC maturation trajectories, uncovering intrinsic and extrinsic profiles, including key maturation drivers. Our findings enhance understanding of retinal development, providing a valuable reference tool for automated annotation and developmental analyses.
Unraveling the developmental heterogeneity of human retinal ganglion cells within the developing retina to study to the continuity of maturation
Emil Kriukov, Jonathan R. Soucy, Everett Labrecque, Petr Baranov | Developmental Biology | 2025
J. Oswald, P. Baranov | Ther Adv Ophthalmol. | 2018
Regenerative medicine in the retina: from stem cells to cell replacement therapy
Following the fast pace of the growing field of stem cell research, retinal cell replacement is finally emerging as a feasible mean to be explored for clinical application. Although neuroprotective treatments are able to slow the progression of retinal degeneration caused by diseases such as age-related macular degeneration and glaucoma, they are insufficient to fully halt disease progression and unable to recover previously lost vision.
A slow-release cocktail of BDNF and GDNF markedly improves outcomes for stem-cell–derived retinal ganglion cell (RGC) therapy. In culture, the factors boosted RGC differentiation, survival, and spontaneous activity; in mouse optic-neuropathy models, co-treatment increased donor RGC survival ~2.7× (mouse→mouse) and ~15× (human→mouse) and also preserved host RGC function. The work shows that engineering the retinal microenvironment with sustained neurotrophic support can both protect vision and make RGC transplantation far more effective, offering a practical adjunct for glaucoma and other optic neuropathies across mild to severe disease stages.
Sustained Neurotrophic Factor Co-Treatment Enhances Donor and Host Retinal Ganglion Cell Survival in Mice
Jonathan R. Soucy; Julia Oswald; Emil Kriukov; Monichan Phay; John Masland; Christian Pernstich; Petr Baranov | TVST | 2025