The long-term objective of this proposal is to determine if in vitro-derived retinal progenitor cells can be used as a form of treatment for retinal diseases. The irreversible loss of photoreceptors is the cause of blindness in many inherited retinal diseases. To address this problem, retinal progenitor cells may have the potential to generate these once thought irreplaceable cells. We have developed an in vitro method of deriving a form of retinal progenitors;we call induced-multipotent retinal cells (iRC). iRCs are sufficient to generate mature retinal cell classes in vitro, and also functional eyes in vivo. The goals of my study are to determine if iRCs can generate mature retinal cell classes in a normal and degenerated mature retina.
The specific aims are Aim 1: Determine the fate of iRCs transplanted into the mature retina. I will first determine if transplanted iRCs can survive, differentiate into retinal cell classes, and structurally integrate into a mature retina.
Aim 2 : Determine the fate of iRCs in a degenerated retina. I will first determine the conditions to maintain a rod- deficient retina in transgenic Xenopus. Next, I will transplant iRCs into the rod-deficient retina and determine if they survive, differentiate, and structurally integrate. The fate of iRCs will be determined using a criterion for cell morphology, immunohistochemistry, and location within the retina. The rationale for these experiments is that identification of the cell classes derived from iRCs will set the foundation for influencing iRCs to differentiate primarily toward the rod photoreceptor fate and testing for any functional improvement in scotopic (rod specific) vision. Determining if iRCs can generate mature retinal cell classes in a normal and degenerated mature retina will pave the way for understanding how to develop therapies for retinal diseases that cause blindness.

Public Health Relevance

Diseases affecting the neural retina are one of the leading causes of impaired vision in the United States. My project will contribute to understanding how to develop new therapies to treat these diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31EY020114-02
Application #
8142875
Study Section
Special Emphasis Panel (ZRG1-IMST-D (29))
Program Officer
Greenwell, Thomas
Project Start
2010-08-23
Project End
2014-08-22
Budget Start
2011-08-23
Budget End
2012-08-22
Support Year
2
Fiscal Year
2011
Total Cost
$30,902
Indirect Cost
Name
Upstate Medical University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210