GLAUCOMATOUS OPTIC NERVE DAMAGE

Research project

Description

Glaucoma is a major cause of blindness in which optic nerve fibers die in
a characteristic pattern. Although many factors may influence this
process, elevated intraocular pressure (IOP) is the best documented and
all glaucoma therapy is directed at controlling eye pressure. In spite
of this, relatively little is known about the neuronal and glial cell
response to elevated IOP, due in large part to the lack of a reliable,
inexpensive animal model of pressure-induced optic nerve damage. Such a model has recently been created in rats. Selective injection of
sclerosing agents into ocular surface vessels using a specially designed
microneedle causes scarring of the aqueous humor outflow pathways,
producing measurably increased IOP and identifiable optic nerve fiber
death. This proposal will refine the technique to produce mild and
severe pressure rises in separate groups of animals. The associated
nerve damage will be studied using histology, automated nerve fiber
counts and immunohistochemistry to demonstrate its relationship to human
glaucomatous optic neuropathy. Efforts to analyze the cellular response to elevated IOP in the mammalian
optic nerve and retina will begin by studying changes in protein presence
and distribution using immunohistochemistry for a variety of well
characterized neuronal and glial cell components, most of which have been
shown to change in response to injury. Initial studies will concentrate
on eyes with severe IOP elevation. Protein changes detected will then be
confirmed and clarified using in situ hybridization with either synthetic
oligodeoxynucleotide probes, or riboprobes, to detect evidence for
cellular changes in message production. Northern blot analysis will also
be used to provide semiquantitative analyses, where indicated, although
their primary use will be in verifying probe specificity. Once reliable changes in specific proteins are defined in eyes with
severe IOP elevation, these markers will be used to clarify the exact
role of IOP in causing nerve damage by comparing eyes with mild and
severe IOP elevations and comparing the effects of early versus prolonged
IOP rise. These studies win serve to establish these changes as markers
for future studies of the other factors that influence the glaucomatous
process, how they affect optic nerve susceptibility to IOP and how they
might be altered to protect the optic nerve in glaucoma.
StatusActive
Effective start/end date4/1/933/31/18

Funding

  • National Institutes of Health: $375,187.00
  • National Institutes of Health
  • National Institutes of Health: $648,783.00
  • National Institutes of Health: $226,726.00
  • National Institutes of Health: $377,500.00
  • National Institutes of Health: $612,036.00
  • National Institutes of Health: $366,638.00
  • National Institutes of Health: $382,844.00
  • National Institutes of Health: $612,037.00
  • National Institutes of Health: $368,994.00
  • National Institutes of Health
  • National Institutes of Health: $717,964.00
  • National Institutes of Health: $77,822.00
  • National Institutes of Health: $377,500.00
  • National Institutes of Health: $377,500.00
  • National Institutes of Health: $171,673.00
  • National Institutes of Health: $208,673.00
  • National Institutes of Health
  • National Institutes of Health: $363,401.00

Fingerprint

Optic Nerve
Intraocular Pressure
Glaucoma
Retinal Ganglion Cells
Pressure
Nerve Growth Factors
Genes
Atrophy
Optic Disk
Wounds and Injuries
Reverse Transcriptase Polymerase Chain Reaction
Axonal Transport
Ischemia
Gene Expression
Cell Survival
Nerve Fibers
Retina
Axons
Cell Death
trkB Receptor

Keywords

  • Medicine(all)