Developing Extracellular Matrix Technology to Treat Retinal or Optic Nerve Injury(1,2,3).

Yolandi van der Merwe,Michael B. Steketee,Tanchen Ren

doi:10.1523/eneuro.0077-15.2015

Abstract

Adult mammalian CNS neurons often degenerate after injury, leading to lost neurologic functions. In the visual system, retinal or optic nerve injury often leads to retinal ganglion cell axon degeneration and irreversible vision loss. CNS axon degeneration is increasingly linked to the innate immune response to injury, which leads to tissue-destructive inflammation and scarring. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling, over scarring, in various tissues and organs, including the peripheral nervous system. However, applying ECM technology to CNS injuries has been limited and virtually unstudied in the visual system. Here we discuss advances in deriving fetal CNS-specific ECMs, like fetal porcine brain, retina, and optic nerve, and fetal non-CNS-specific ECMs, like fetal urinary bladder, and the potential for using tissue-specific ECMs to treat retinal or optic nerve injuries in two platforms. The first platform is an ECM hydrogel that can be administered as a retrobulbar, periocular, or even intraocular injection. The second platform is an ECM hydrogel and polymer “biohybrid” sheet that can be readily shaped and wrapped around a nerve. Both platforms can be tuned mechanically and biochemically to deliver factors like neurotrophins, immunotherapeutics, or stem cells. Since clinical CNS therapies often use general anti-inflammatory agents, which can reduce tissue-destructive inflammation but also suppress tissue-reparative immune system functions, tissue-specific, ECM-based devices may fill an important need by providing naturally derived, biocompatible, and highly translatable platforms that can modulate the innate immune response to promote a positive functional outcome.

Highlights

2.5 million cases of ocular trauma are reported annually in the United States, with about 50,000 of these cases resulting in permanent vision loss at an estimated lifetime cost of approximately $900,000 per person according to the National Federation of the Blind (2013)
Though this review focuses primarily on the retinal ganglion cells (RGCs), microglia, and macrophages, the potential benefits of Extracellular matrix (ECM) technology are widely applicable to other neural and glial populations throughout the CNS
Studies from animals that can regenerate CNS tissues, including retina, optic nerve, and brain, indicate that the temporal and spatial organization of macrophage phenotypes is a critical determinant in the overall healing response (Shechter et al, 2009, 2013)

Summary

Introduction

2.5 million cases of ocular trauma are reported annually in the United States, with about 50,000 of these cases resulting in permanent vision loss at an estimated lifetime cost of approximately $900,000 per person according to the National Federation of the Blind (2013). Extracellular matrix (ECM) technology has been widely successful clinically in modulating the innate response of the immune system to reduce inflammation and to increase positive tissue remodeling, over scarring.

Results

Conclusion