Mishal Rao

All Publications

• Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration. Acta neuropathologica communications Rao, M., Luo, Z., Liu, C. C., Chen, C. Y., Wang, S., Nahmou, M., Tanasa, B., Virmani, A., Byrne, L., Goldberg, J. L., Sahel, J. A., Chang, K. C. 2024; 12 (1): 204

  Abstract

  Mammalian central nervous system (CNS) axons cannot spontaneously regenerate after injury, creating an unmet need to identify molecular regulators to promote axon regeneration and reduce the lasting impact of CNS injuries. While tubulin polymerization promoting protein family member 3 (Tppp3) is known to promote axon outgrowth in amphibians, its role in mammalian axon regeneration remains unknown. Here we investigated Tppp3 in retinal ganglion cells (RGCs) neuroprotection and axonal regeneration using an optic nerve crush (ONC) model in the rodent. Single-cell RNA sequencing identified the expression of Tppp3 in RGCs of mice, macaques, and humans. Tppp3 overexpression enhanced neurite outgrowth in mouse primary RGCs in vitro, promoted axon regeneration, and improved RGC survival after ONC. Bulk RNA sequencing indicated that Tppp3 overexpression upregulates axon regeneration genes such as Bmp4 and neuroinflammatory pathways. Our findings advance regenerative medicine by developing a new therapeutic strategy for RGC neuroprotection and axon regeneration.

  View details for DOI 10.1186/s40478-024-01917-6

  View details for PubMedID 39734233

  View details for PubMedCentralID 8931466

• A potential therapeutic target for optic nerve regeneration Rao, M., Luo, Z., Liu, C., Nahmou, M., Tanasa, B., Virmani, A., Byrne, L., Goldberg, J., Sahel, J., Chang, K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001312227707102

• Aldose reductase inhibition decelerates optic nerve degeneration by alleviating retinal microglia activation. Scientific reports Rao, M., Huang, Y. K., Liu, C. C., Meadows, C., Cheng, H. C., Zhou, M., Chen, Y. C., Xia, X., Goldberg, J. L., Williams, A. M., Kuwajima, T., Chang, K. C. 2023; 13 (1): 5592

  Abstract

  As part of the central nervous system (CNS), retinal ganglion cells (RGCs) and their axons are the only neurons in the retina that transmit visual signals from the eye to the brain via the optic nerve (ON). Unfortunately, they do not regenerate upon injury in mammals. In ON trauma, retinal microglia (RMG) become activated, inducing inflammatory responses and resulting in axon degeneration and RGC loss. Since aldose reductase (AR) is an inflammatory response mediator highly expressed in RMG, we investigated if pharmacological inhibition of AR can attenuate ocular inflammation and thereby promote RGC survival and axon regeneration after ON crush (ONC). In vitro, we discovered that Sorbinil, an AR inhibitor, attenuates BV2 microglia activation and migration in the lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) treatments. In vivo, Sorbinil suppressed ONC-induced Iba1 + microglia/macrophage infiltration in the retina and ON and promoted RGC survival. Moreover, Sorbinil restored RGC function and delayed axon degeneration one week after ONC. RNA sequencing data revealed that Sorbinil protects the retina from ONC-induced degeneration by suppressing inflammatory signaling. In summary, we report the first study demonstrating that AR inhibition transiently protects RGC and axon from degeneration, providing a potential therapeutic strategy for optic neuropathies.

  View details for DOI 10.1038/s41598-023-32702-5

  View details for PubMedID 37019993

  View details for PubMedCentralID PMC10076364

• Aldose reductase inhibition promotes retinal ganglion cell survival after optic nerve injury Rao, M., Huang, Y., Meadows, C., Liu, C., Cheng, H., Zhou, M., Cheng, Y., Xia, X., Goldberg, J. L., Kuwajima, T., Chang, K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401304279