Combinatorial Therapy Stimulates Long-Distance Regeneration, Target Reinnervation, and Partial Recovery of Vision After Optic Nerve Injury in Mice - International Review of Neurobiology - page 151

CHAPTER SIX

Combinatorial Therapy Stimulates
Long-Distance Regeneration,
Target Reinnervation, and Partial
Recovery of Vision After Optic
Nerve Injury in Mice

, † ,}, } ,1
* Laboratories for Neuroscience Research in Neurosurgery and F.M. Kirby Neurobiology Center, Children's
Hospital, Boston, Massachusetts, USA
† Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA
‡ Program of Basic and Clinical Neuroscience, Institute of Biomedical Sciences, Centre of Health Sciences,
Universidade Federal do, Rio de Janeiro, Brazil
} Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
} Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
1 Corresponding author: e-mail address: [e-mail]

, † , ‡ , Ghaith Habboub * , † , Larry I. Benowitz *

Silmara de Lima *

Contents
1. Intraocular Inflammation Promotes Optic Nerve Regeneration 154

2. Oncomodulin Plays a Central Role in Inflammation-Induced Regeneration 155

3. Stimulating Optic Nerve Regeneration by Activating Cell Signaling Pathways 158

4. Synergy Between Activating RGCs ' Intrinsic Growth State and Counteracting Cell-
Extrinsic Inhibitors of Growth 160

5. Synergy Between Intraocular Inflammation and Deleting Suppressors of Cell
Signaling

161

6. RGC Survival 164

7. Partial Return of Simple Visual Behaviors 165

8. Conclusions 167

Acknowledgments 167

References 167

Abstract
The optic nerve has been widely studied for insights into mechanisms that suppress or
promote axon regeneration after central nervous system injury. Following optic nerve
damage in adult mammals, retinal ganglion cells (RGCs) normally fail to regenerate their
axons, resulting in blindness in patients who suffer from neurodegenerative diseases
such as glaucoma or who have sustained traumatic injury to the optic nerve. Over
the past several decades, many groups have investigated the basis of regenerative fail-
ure in the hope of developing strategies to stimulate the regrowth of axons and restore