Abstract

We propose to investigate the metabolism of cyclic nucleotides in cone visual cells of the 13-line ground squirrel and in diseased cones of the Alaskan malamute dog that is affected by an inherited retinal degeneration. Metabolism will be assessed by measuring the content of cAMP and cGMP, and the activity of the corresponding synthetic and degradative enzymes. Kinetic characteristics and mechanisms for activation or inhibition of the respective cyclases or phosphodiesterases will be studied. A link between cyclic nucleotide metabolism and visual pigment bleaching will be explored by measuring whether light produces an alteration in cyclic nucleotide levels of cone visual cells. Modulation of cone metabolism by cyclic nucleotides may occur through the controlled phosphorylation of specific proteins and such a mechanism will be studied using isolated cone outer segments. This systemic study of cyclic nucleotide metabolism is designed to produce insights into the control of cone metabolism or function and to further our understanding of cone degeneration.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002651-08
Application #
3256968
Study Section
(VID)
Project Start
1978-08-01
Project End
1986-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Verardo, Mark R; Viczian, Andrea; Piri, Natik et al. (2009) Regulatory sequences in the 3' untranslated region of the human cGMP-phosphodiesterase beta-subunit gene. Invest Ophthalmol Vis Sci 50:2591-8
Souied, Eric H; Reid, Silvia N M; Piri, Natik I et al. (2008) Non-invasive gene transfer by iontophoresis for therapy of an inherited retinal degeneration. Exp Eye Res 87:168-75
Gao, Yong-Qing; Danciger, Michael; Ozgul, Riza Koksal et al. (2007) Association of the Asn306Ser variant of the SP4 transcription factor and an intronic variant in the beta-subunit of transducin with digenic disease. Mol Vis 13:287-92
Tsang, S H; Woodruff, M L; Janisch, Kerstin M et al. (2007) Removal of phosphorylation sites of gamma subunit of phosphodiesterase 6 alters rod light response. J Physiol 579:303-12
Lerner, Leonid E; Piri, Natik; Farber, Debora B (2006) Transcriptional and post-transcriptional regulation of the rod cGMP-phosphodiesterase beta-subunit gene. Recent advances and current concepts. Adv Exp Med Biol 572:217-29
Tsang, Steven H; Woodruff, Michael L; Chen, Ching-Kang et al. (2006) GAP-independent termination of photoreceptor light response by excess gamma subunit of the cGMP-phosphodiesterase. J Neurosci 26:4472-80
Lerner, Leonid E; Peng, Guang-Hua; Gribanova, Yekaterina E et al. (2005) Sp4 is expressed in retinal neurons, activates transcription of photoreceptor-specific genes, and synergizes with Crx. J Biol Chem 280:20642-50
Linberg, Kenneth A; Fariss, Robert N; Heckenlively, John R et al. (2005) Morphological characterization of the retinal degeneration in three strains of mice carrying the rd-3 mutation. Vis Neurosci 22:721-34
Piri, Natik; Gao, Yong Qing; Danciger, Michael et al. (2005) A substitution of G to C in the cone cGMP-phosphodiesterase gamma subunit gene found in a distinctive form of cone dystrophy. Ophthalmology 112:159-66
Viczian, A S; Verardo, M; Zuber, M E et al. (2004) Conserved transcriptional regulation of a cone phototransduction gene in vertebrates. FEBS Lett 577:259-64

Showing the most recent 10 out of 77 publications