Deciphering Proteins and their Functions in the Regenerating Retina

Verena Prokosch; Carolin Chiwitt; Karin Rose; Solon Thanos

Disclosures

Expert Rev Proteomics. 2010;7(5):775-795. 

In This Article

Abstract and Introduction

Abstract

Neurons of the mammalian CNS, including retinal ganglion cells, lack, in contrast to the PNS, the ability to regenerate axons spontaneously after injury. Regeneration of the CNS is extremely complex and involves various molecular factors and cells. Therewith the regenerative process remains an enormous scientific and clinical challenge. This article provides an overview of proteins that play a crucial role in axon regeneration of retinal ganglion cells and their underlying signaling pathways. In this context, we elucidate the role of 2D gel electrophoresis and highlight some additional proteins, altered upon regeneration by using this highly sensitive method.

Introduction

Neurons of the adult mammalian CNS, including retinal ganglion cells (RGCs), are unable to regenerate axons spontaneously after injury. This contrasts with the vigorous regeneration of peripheral axons, enabling them to regrow and re-establish functional connections. Organisms above lower vertebrates, such as fish and amphibians, show extensive regeneration of axons and recovery of function.

The regenerative ability within the mammalian CNS implying growth-cone formation, axonal guidance and synaptogenesis declines during development and ends during postnatal life. During early development, axons form an intricate and complex web of connections through a highly regulated guidance process.[1] Upon the completion of development, neuron plasticity decreases dramatically, close to zero, as first noted by Ramon y Cajal.[2] Most likely, this failure is attributable to two main elements: the downregulation of growth-related genes and proteins resulting in a poor intrinsic ability for neurons to regenerate and the expression of growth-inhibiting proteins by glial cells and/or other components of the CNS.

The better understanding of the mechanisms associated with neuron injury, the subsequent apoptosis and regenerative failure remains an enormous scientific and clinical challenge. In spite of their failure to regenerate axons within their inhospitable environment, CNS neurons and in particular RGCs can regain the ability to build out growth cones and regenerate axons under certain experimental conditions in vivo and in vitro, thereby demonstrating that they retain the genetic pool coding for regeneration-related proteins, although axonal guidance and synaptogenesis is still poorly understood.

This article provides an overview of proteins that play a crucial role in axon regeneration of RGCs and the underlying signaling pathways, elucidates the role of 2D gel electrophoresis (2-DE) in this context and highlights some additional altered proteins by using this highly sensitive method.

processing....