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Abstract #104899 Published in IGR 23-2
Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes
Li L; Fang F; Feng X; Zhuang P; Huang H; Liu P; Liu L; Xu AZ; Qi LS; Cong L; Hu YNeuron 2022; 110: 2646-2663.e6
Axon regeneration holds great promise for neural repair of CNS axonopathies, including glaucoma. Pten deletion in retinal ganglion cells (RGCs) promotes potent optic nerve regeneration, but only a small population of Pten-null RGCs are actually regenerating RGCs (regRGCs); most surviving RGCs (surRGCs) remain non-regenerative. Here, we developed a strategy to specifically label and purify regRGCs and surRGCs, respectively, from the same Pten-deletion mice after optic nerve crush, in which they differ only in their regeneration capability. Smart-Seq2 single-cell transcriptome analysis revealed novel regeneration-associated genes that significantly promote axon regeneration. The most potent of these, Anxa2, acts synergistically with its ligand tPA in Pten-deletion-induced axon regeneration. Anxa2, its downstream effector ILK, and Mpp1 dramatically protect RGC somata and axons and preserve visual function in a clinically relevant model of glaucoma, demonstrating the exciting potential of this innovative strategy to identify novel effective neural repair candidates.
Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
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