Manipulating Kruppel-Like Factors for RGC Regeneration

Jeffrey Goldberg, MD, PhD University of Miami Miller School of Medicine


As a result of glaucoma, retinal ganglion cells (RGC) axons are damaged in the optic nerve head, and fail to regenerate through the optic nerve. Here we study methods to enhance RGCs' intrinsic capacity for optic nerve regeneration through manipulation of the KLF" family of transcription factors using a gene therapy approach. Enhancing optic nerve regeneration may enhance recovery from glaucomatous optic nerve damage."

Project Details

In glaucoma, the optic nerve becomes damaged and fails to regenerate. Because the optic nerve is the only connection between the eye and the brain, this failure of regeneration causes permanent vision loss. We have recently discovered a group of genes called Kruppel-Like Factors (KLFs) that appear to control optic nerve regeneration; this work was published in the journal “Science”. In these experiments, we test whether we can enhance optic nerve regeneration further with gene therapy to manipulate multiple KLFs. In Aim 1 we are building special gene therapy technology that can deliver KLFs to retinal ganglion cells, the neurons in the eye that normally project through the optic nerve. In Aim 2 we test these vectors in an animal model of optic nerve degeneration, to see if they further enhance regeneration. If successful, this will represent a new approach to treating glaucoma and to restoring lost vision.

Jeffrey Goldberg is a physician-scientist who studies the survival and regeneration of retinal ganglion cells in the lab, in addition to seeing patients with glaucoma in his clinical practice.