Our long-term goal is to define the roles of retinoids in the visual transduction process and to explore the potential of retinal analogs in treating disorders resulting from improper retinoid processing, such as in Leber's amaurosis. Our working premise is that the retinal chromqphore (11-cis retinal) controls the biochemical and physiological properties of visual pigments.
Our first aim i s to investigate the structural determinants in opsins that modulate retinal interactions. Studies will determine: 1) if the unique red cone opsin properties are due to the absence of a palmitate group anchoring the C-terminus of the protein, 2) if a putative secondary retinoid binding site on opsins exists and its integrity of is dependent on the presence of a palmitate, and 3) if all-trans retinol formation and clearance from the outer segment are controlled by structural features of opsins, the opsin/retinoid interactions and photoreceptor morphology.
Our second aim i s to investigate the role of retinoid cycling in rod and cone degeneration. Studies will determine: 1) if rod opsin phosphorylation slows the degeneration arising from opsin activity in models that lack 11-cis retinal, 2) if improper vitamin A processing leads to cone opsin mislocalization and eventual cones degeneration, and 3) if light-stable, analogues of 11-cis retinal can correct this cone opsin mislocalization and prevent cone degeneration. We anticipate that these studies will form a rational basis for using retinoid-like compounds to treat the blinding diseases that result from improper vitamin A processing. The retinoid, vitamin A, is known to be essential for vision. Lack of adequate vitamin A for the visual process can arise from dietary deficiency or through a failure of processing this compound properly. We are studying the processing of vitamin A in the eye and exploring the pharmaceutical potential of using retinoid-like compounds to treat diseases resulting from improper processing of vitamin A.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004939-27
Application #
7802104
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Mariani, Andrew P
Project Start
1983-08-01
Project End
2013-03-31
Budget Start
2010-04-01
Budget End
2013-03-31
Support Year
27
Fiscal Year
2010
Total Cost
$431,236
Indirect Cost
Name
Medical University of South Carolina
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Bowrey, Hannah E; Anderson, David M; Pallitto, Patrick et al. (2016) Imaging mass spectrometry of the visual system: Advancing the molecular understanding of retina degenerations. Proteomics Clin Appl 10:391-402
Tang, Peter H; Crouch, Rosalie K (2015) Sustained delivery of retinoids to prevent photoreceptor death. Methods Mol Biol 1271:363-8
Crouch, Rosalie K; Koutalos, Yiannis; Kono, Masahiro et al. (2015) A2E and Lipofuscin. Prog Mol Biol Transl Sci 134:449-63
Ablonczy, Zsolt; Smith, Noah; Anderson, David M et al. (2014) The utilization of fluorescence to identify the components of lipofuscin by imaging mass spectrometry. Proteomics 14:936-44
Ablonczy, Zsolt; Higbee, Daniel; Grey, Angus C et al. (2013) Similar molecules spatially correlate with lipofuscin and N-retinylidene-N-retinylethanolamine in the mouse but not in the human retinal pigment epithelium. Arch Biochem Biophys 539:196-202
Tang, Peter H; Kono, Masahiro; Koutalos, Yiannis et al. (2013) New insights into retinoid metabolism and cycling within the retina. Prog Retin Eye Res 32:48-63
Ablonczy, Zsolt; Higbee, Daniel; Anderson, David M et al. (2013) Lack of correlation between the spatial distribution of A2E and lipofuscin fluorescence in the human retinal pigment epithelium. Invest Ophthalmol Vis Sci 54:5535-42
Bandyopadhyay, Mausumi; Kono, Masahiro; Rohrer, Bärbel (2013) Explant cultures of Rpe65-/- mouse retina: a model to investigate cone opsin trafficking. Mol Vis 19:1149-57
Frederiksen, Rikard; Boyer, Nicholas P; Nickle, Benjamin et al. (2012) Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and dark adaptation in salamander rods. J Gen Physiol 139:493-505
Boyer, Nicholas P; Tang, Peter H; Higbee, Daniel et al. (2012) Lipofuscin and A2E accumulate with age in the retinal pigment epithelium of Nrl-/- mice. Photochem Photobiol 88:1373-7

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