Cellular and molecular mechanisms of retinal regeneration in the axolotl salamander

Abstract

Degenerative disorders of the retina cause progressive and extensive deterioration of retinal neurons. Humans cannot recover from this damage and face lifelong eyesight impairment. By contrast, some lower vertebrate species can regenerate their retinas. Understanding the cellular and molecular mechanisms of regeneration is crucial for developing therapies that will extend retinal recovery to humans. In Chapter 1, we summarize the current state of literature on retinal regeneration. The Mexican axolotl is an advantageous model of neural regeneration. This highly regenerative salamander can repair the spinal cord and portions of the brain even in adulthood. As a tetrapod amphibian, it is more evolutionarily proximal to humans than zebrafish - a popular model of retinal regeneration. It is more amenable to genetic manipulations than newts, another model of retinal regeneration, as not only has the axolotl genome been sequenced, but this salamander also breeds readily in laboratories. In Chapter 2, we describe how to establish and care for an axolotl laboratory research facility. In Chapter 3, we show that compared to the mammalian retina, the axolotl retina harbors pro-regenerative properties. Despite these advantages, the current understanding of axolotl retinal regeneration is limited. Young axolotls regenerate both retinas and lenses but lose the ability to regenerate lenses as they mature, so it cannot be assumed that their ability for retinal regeneration persists into adulthood. In Chapter 4, we describe the development of a retinal injury model for adult axolotls. In Chapter 5, we demonstrate that adult axolotls can successfully regenerate injured retinas. We also show some specific molecular mechanisms that enable this amazing feat of regeneration.--Author's abstract