The long term objective of this proposal is to enhance the understanding of the mechanism by which retinal ganglion cell (RGC) death occurs upon exposure to elevated intraocular pressure in order to open up new strategies for treatment of glaucoma. While there is general agreement that RGCs are primarily affected by glaucoma, there is only limited information about the effects of the disease on other retinal cells. In particular, the interactions between retinal glia and RGCs are poorly understood. The major focus of the present proposal is on such interactions which may be of crucial importance for both the survival and death of RGCs. Preliminary experiments suggest that retinal glia respond to elevated intraocular pressure (IOP) with upregulation of the gap junction protein connexin50 synthesis which could alter the communication patterns amongst glia as well as between glia and RGCs. Additionally, proliferation of Cx50-like immunoreactive putative astrocytes in the optic nerve head has been observed which may explain the typical cupping of the optic disc in glaucoma.
The specific aims of this proposal are to identify the cellular mechanisms involved in the overexpression of Cx50 in relation to other glial markers and to markers for cell proliferation such as BrdU and PCNA. A possible contribution of microglia to the suggested gliosis will be studied by counterstaining retinal sections for Ox42, a specific microglial marker. To control for RGC-death, sections will be counterstained with YOYO-1 and ApopTaq, markers for apoptotic cells. Altogether, the experiments proposed will help to understand glia-neuron interactions which may be instrumental in preventing and/or inducing selective loss of RGCs in glaucoma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29EY011995-01A1
Application #
2697091
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1998-07-01
Project End
2003-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029