# Identification of a novel pathway that regulates optic nerve myelination and remy > **NIH NIH R00** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $83,023 ## Abstract Project Summery In the optic nerve, oligodendrocytes (OLs) are sole myelin-producing cells. Myelin provides insulation and trophic support for RGC axons and allows for normal vision. Death of OLs and demyelination in the optic nerve are the hallmarks of demyelinating diseases that often impair vision, including optic neuritis and multiple sclerosis. The signaling mechanisms that controls OL survival and demyelination are still poorly understood. Previous studies have identified a myriad of extracellular cues and OL cell surface receptors that mediate OL survival and differentiation but the intrinsic pathways that link these trophic cues to downstream events remain elusive. In my previous studies, I made a striking discovery by identifying the Transcription Factor EB (TFEB) as the missing link. I discovered that TFEB is highly expressed by OL lineage cells in the CNS including the optic nerve. I generated a novel TFEB conditional mouse line and showed that in the mouse brain TFEB powerfully antagonizes myelination by promoting premyelinating OL cell apoptosis and simultaneously inhibiting OL maturation. Based on these findings, I propose to test the hypotheses that TFEB serves as the critical sensor in premyelinating OLs that facilitates cell apoptosis in the absence of axonal contact or trophic support, and that TFEB regulates the autophagy pathway to control OL maturation and myelination. I will utilize the rodent optic nerve as a model system to test these hypotheses. In my K99 phase, I have determined the expression and function of TFEB in developing myelination in the rodent optic nerves, and I have addressed the molecule mechanisms through which TFEB promotes premyelinating OL cell death. In addition, I gained training in animal surgery and mouse visual behavioral assays in my co-mentor's laboratory. As an independent investigator, I will leverage the expertise and techniques that I have acquired in my K99 phase to comprehensively investigate TFEB function in optic nerve myelination, and to determine its roles in myelin repair in optic neuritis animal models. Specifically, my laboratory will utilize cell-type specific TFEB conditional mutants that I have already generated to genetically dissect out the roles of TFEB in OL development and myelination. We will perform whole-genome RNA sequencing experiments to identify the candidate pathways that TFEB regulates in myelinating OLs, and further investigate one candidate pathway, the autophagy pathway in controlling myelination. Finally, we will determine the function of TFEB pathway in optic nerve demyelination and remyelination, and further modulate the TFEB pathway to promote vision recovery in optic neuritis animal models. The proposed research will characterize a novel pathway regulating optic nerve myelination and will determine the underlying mechanisms. By developing new drugs that target the TFEB pathway, our goal is to lessen optic nerve damage and promote remyelination and visual reco... ## Key facts - **NIH application ID:** 10440233 - **Project number:** 3R00EY029330-04S1 - **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER - **Principal Investigator:** Lu Sun - **Activity code:** R00 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $83,023 - **Award type:** 3 - **Project period:** 2020-07-01 → 2023-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10440233 ## Citation > US National Institutes of Health, RePORTER application 10440233, Identification of a novel pathway that regulates optic nerve myelination and remy (3R00EY029330-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440233. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*