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Michael Granato, PhD
dr. granato investigates SPONTANEOUS OPTIC NERVE REGENERATION IN ZEBRAFISH By Rebecca Salowe
Michael Granato, PhD, Professor of Cell and Developmental Biology, is conducting groundbreaking research on spontaneous regeneration of the optic nerve. A vision scientist at the University of Pennsylvania, he has received two R01 grants from the National Eye Institute to investigate this poorly understood topic. In mammals, the central nervous system (CNS) has a minimal capacity for regeneration. The CNS includes the retina and the optic nerve, which is made up of axons from retinal ganglion cells (RGCs). These axons extend from the retina to the brain and associated glia. When the optic nerve becomes damaged in diseases such as glaucoma, the injury can lead to irreversible vision loss and blindness due to the limited capacity of the optic nerve for regeneration. Amphibians and fish, on the other hand, have a remarkable capacity for optic nerve regeneration following injury. As a result, these animals are often used as model systems to study injury to the CNS. “Zebrafish in particular are a productive model for spontaneous spinal cord regeneration, as well as optic nerve regeneration,” said Dr. Granato. There are many unanswered questions about regeneration. Models such as zebrafish can be used to understand how
optic nerve axons and surrounding glia interact during optic nerve regeneration. For example, how are immune and glia cells summoned to the injury site, and how do they provide guidance to regenerate RGCs? Prior research in this area has uncovered several intrinsic neural signaling pathways that boost axonal growth of injured RGCs and suppress cell death. However, this growth is frequently characterized by axonal misguidance and limited functional regeneration. This limitation spurred Dr. Granato’s interest in studying how guidance cues and underlying cellular mechanisms play a role in optic nerve regeneration. “Which extrinsic cues and guidance pathways ensure correct RGC guidance during regeneration is unclear,” said Dr. Granato. “Identifying these cues, and the underlying cellular mechanisms, appears paramount to achieving functional optic nerve regeneration.” A large reason for these gaps in knowledge is due to challenges in live cell imaging in mammals. Dr. Granato sought to fill this void by investigating the cellular and molecular pathways of spontaneous optic nerve regeneration in larval zebrafish. He received an R01 grant
