The Transcription Factor 12 of Basic Helix-Loop-Helix Plays an Essential Role in Retinal Health
Tian Yu1,2, Gizem Ulker-Yilmazer1, Dogan Can Kirman1
1Department of Ophthalmology, UT Southwestern Medical Center, Dallas, Texas, United States.
Investigative Ophthalmology & Visual Science
|May 7, 2026
Summary
Transcription factor TCF12 (Tcf12) deficiency causes early retinal structural changes and later functional decline. This study highlights Tcf12
Area of Science:
- Ophthalmology and Vision Science
- Genetics and Molecular Biology
- Neuroscience
Background:
- The transcription factor TCF12 plays a role in cellular development and differentiation.
- Its specific function in maintaining retinal health and homeostasis is not fully understood.
Purpose of the Study:
- To investigate the non-redundant role of Tcf12 in retinal health and function.
- To elucidate the molecular mechanisms underlying Tcf12-associated retinal alterations.
Main Methods:
- Utilized optical coherence tomography (OCT) and a forward genetic screen to identify Tcf12 loss-of-function.
- Generated CRISPR/Cas9 Tcf12ra/ra mice for validation, assessing retinal morphology (OCT, fundus photography, histology) and function (electroretinography).
- Performed bulk RNA sequencing and proteomic analyses, validating key targets with RT-qPCR and immunoblotting.
Main Results:
- Tcf12ra/ra mice exhibited early outer nuclear layer thinning and age-dependent retinal spot accumulation.
- Observed late-onset subretinal microglial activation and electroretinography deficits (12-15 months).
- Transcriptomic and proteomic analyses revealed widespread dysregulation in metabolic, signaling, and inflammatory pathways.
Conclusions:
- Tcf12 deficiency induces early structural and late functional deficits in the retina.
- Dysregulation of metabolic and signaling pathways is a key consequence of Tcf12 loss.
- Establishes Tcf12 as a critical factor in retinal development and homeostasis.
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