Glaucoma is a leading causes of blindness and along with other optic neuropathies is characterized by the loss of retinal ganglion cells (RGCs). Increased intraocular pressure (IOP) management is the current standard of care for glaucoma patients, but fails to stop the irreversible loss of RGCs and progressive visual dysfunction. Vision restoration through RGC replacement therapy, one of the NEI?s Audacious Goals program, could be a potential solution, and considerable progress has been made in understanding the molecular signals that regulate RGC specification from human stem cells, as well as in RGC transplant and integration in rodents. However, when considering translation of laboratory advances to human testing, rodent models are limited by critical differences in retinal physiology, and proof-of-concept in non-human primates would greatly increase confidence and aid in therapeutic development before moving to human testing. Thus there is a considerable need for a tractable non-human primate model. Here we will establish a squirrel monkey-induced glaucoma model and the parameters to study human stem cell-derived RGC integration and potential vision restoration in a retina and visual system closer to those of human. Through this 5-year proposal we will achieve critical milestones, including validating the monkey glaucoma model, studying key structural and functional measures using innovative new modalities that should be portable between monkey and humans, and demonstrating the model?s ability to move across institutions. All of this will be accomplished in the setting of studying RGC transplant: differentiation, migration, local integration and synapse formation, growth down the optic nerve, and targeting to distal brain nuclei, with the goal of vision restoration.

Public Health Relevance

Glaucoma is a leading causes of blindness. Here we will establish a squirrel monkey-induced glaucoma model to study human stem cell-derived RGC cell transplant and integration and potential vision restoration in a retina and visual system closer to those of human. Through validating the monkey glaucoma model and studying key structural and functional measures using innovative new modalities that should be portable between monkey and humans, we will take significant steps towards the goal of vision restoration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24EY029903-03
Application #
10016302
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Liberman, Ellen S
Project Start
2018-09-30
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Stanford University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305