Poor regeneration and reconnection of retinal ganglion cell (RGC) axons is a major obstacle for treating ocular trauma and diseases including glaucoma. There are as yet no therapies to repair optic nerve once the damage is done. Our new studies have discovered cohorts of RGCs that have a very high regenerative capacity. Furthermore, we now uncover previously unrecognized ability of distinct lipids to promote axon growth.
In Aim 1, we will use High Content Screening and functionally test various candidate genes for their ability to promote neurite growth.
In Aim 2, we will determine lipid profiles in RGCs, and functionally test neurite growth-promoting effects of select lipids.
In Aim 3, we will use in vivo optic nerve injury model to determine RGC axon regeneration receiving various treatments. Identifying novel targets that further increase RGC axon regeneration to the brain represents a critical future study. Results obtained from these studies will provide invaluable information on developing future therapies to repair degenerated optic nerve.

Public Health Relevance

Poor regeneration and reconnection of retinal ganglion cell (RGC) axons is a major obstacle for repairing damaged optic nerve. This study will combine RNA-seq, High Content Screening, lipidomics and in vivo model of optic nerve injury to reveal new targets that promote optic nerve regeneration. Results obtained from this study will provide invaluable information on developing future therapies to repair degenerated optic nerve.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01EY027257-02
Application #
9340195
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Agarwal, Neeraj
Project Start
2016-09-01
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Ding, Di; Enriquez-Algeciras, Mabel; Valdivia, Anddre Osmar et al. (2018) The Role of Deimination in Regenerative Reprogramming of Neurons. Mol Neurobiol :
Fischer, Dietmar; Harvey, Alan R; Pernet, Vincent et al. (2017) Optic nerve regeneration in mammals: Regenerated or spared axons? Exp Neurol 296:83-88
Suarez, Maria Fernanda; Piqueras, Maria Carmen; Correa, Leandro et al. (2017) Phospholipidomic Studies in Human Cornea From Climatic Droplet Keratopathy. J Cell Biochem 118:3920-3931
Bray, Eric R; Noga, Markus; Thakor, Kinjal et al. (2017) 3D Visualization of Individual Regenerating Retinal Ganglion Cell Axons Reveals Surprisingly Complex Growth Paths. eNeuro 4: