• Barnstable, Colin (PI)
  • Hughes, Thomas (PI)

Project: Research project

Project Details


The long term goals of the work proposed in this application are
to understand receptor mediated events in the ciliary processes
which may be responsible for regulation of the rate of formation
of aqueous humor. Toward this end we propose to study
interactions among beta2-, alpha2-, VIP, ANF, and somatostatin
receptors in regulating cyclic nucleotide production by ciliary
processes and examine the roles of VIP, ANF, and somatostatin in
regulating aqueous flow and IOP. Most of the in vitro
experiments proposed will explore cyclic AMP and cyclic GMP
production by intact, excised rabbit ciliary processes; however,
where significant results are obtained in this model system we
will explore the possibility that similar mechanisms occur in
human ciliary processes. The premise of our long term goals is
that it is only by a thorough understanding of the mechanisms
underlying normal regulation of aqueous flow that we will
understand how some drugs currently used or proposed for use in
glaucoma therapy reduce IOP and will build a logical framework
within which to search for new therapeutic drugs for treatment of
glaucoma. The specific aims of this proposal are to determine 1. Whether alpha2-adrenergic receptors inhibit beta2-adrenergic
receptor mediated cyclic AMP production in human ciliary
2. What is the nature of alpha2-adrenergic receptor-mediated
inhibition of VIP-stimulated cyclic AMP production in rabbit
ciliary processes;
3. What is the nature of somatostatin receptor-mediated
inhibition of beta2-adrenergic and VIP receptor-mediated
stimulation of cyclic AMP production in rabbit ciliary processes;
4. Whether cyclic GMP is the intracellular mediator of the ANF
receptor in ciliary processes and whether ANF inhibits beta2-
adrenergic and VIP receptor mediated cyclic AMP production;
5. Whether the inhibitory effects of alpha2-adrenergic and
somatostatin receptors on cyclic AMP production are mediated by
the guanine nucleotide binding protein Ni;
6. ANF, VIP, or somatostatin regulate aqueous flow and IOP in
7. Whether similar mechanisms identified in rabbit ciliary
processes (#2-4) occur in human ciliary processes.
Effective start/end date12/31/896/30/00


  • National Eye Institute
  • National Eye Institute
  • National Eye Institute
  • National Eye Institute
  • National Eye Institute
  • National Eye Institute


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