Abstract: A pharmaceutical composition for treating a metabolic disease in a mammalian subject includes a therapeutically effective amount of all-trans-13,14-dihydroretinoid, all-trans-13,14-dihydroretinoid derivative, or agent capable of modulating the level of at least one all-trans-13,14-dihydroretinoid or all-trans-13,14-dihydroretinoid derivative in the subject.

Abstract: In one aspect the present invention provides methods for assessing a physiological state of a mammalian retina in vivo, the methods of this aspect of the invention each include the steps of: (a) irradiating a portion of a mammalian retina, in vivo, with light having a wavelength in the range of from 600 nm to 1000 nm at an intensity sufficient to stimulate two-photon-induced fluorescence in the retina; and (b) assessing a physiological state of the retina by analyzing the fluorescence.

Abstract: A method of treating or preventing age-related retinal dysfunction involves administering to a patient a pharmaceutically effective amount of a synthetic retinal derivative repeatedly over a duration of at least about 3 months. Effective synthetic retinal derivatives include 9-cis-retinyl esters, 11-cis-retinyl esters, derivatives and congeners thereof, and combinations thereof. Suitable ester substituents include carboxylates of C1-C10 monocarboxylic acids and C2-C22 polycarboxylic acids.

Abstract: In one aspect the invention relates to a method for testing a chemical entity for its capability to modulate a (poly)peptide that is malfunctioning by means of an interaction of said chemical entity and said (poly)peptide, the method using single-molecule force spectroscopy. In another aspect the invention relates to a method for testing a chemical or physical entity for its capability to interact with a G protein-coupled receptor (GPCR) in its natural membrane environment, the method using single-molecule force spectroscopy.

Abstract: A method is provided for treating a degenerative disease in a vertebrate eye. A method is further provided for preventing photoreceptor degeneration in a vertebrate eye.

Abstract: Compositions of all-trans-retinol: all-trans-13,14-dihydroretinal saturase and methods of use thereof are provided.

Abstract: Compositions of and methods for using synthetic retinal derivatives as retinoid replacements and opsin agonists are provided.

Abstract: Compositions of and methods for using synthetic retinoids as retinoid replacements and opsin agonists are provided.

Abstract: The present invention relates generally to the preparation and use of retinoid N-retinylidene-N-retinyl-ethanolamine (A2E) conjugated to a carrier polypeptide and to the preparation and use of antibodies that bind specifically to A2E. The invention relates to the use of A2E conjugates as immunogens or vaccines and to the use of A2E specific antibodies for treatment of ophthalmic diseases. Provided herein are methods for enhancing retinal neuronal cell survival, including photoreceptor cell survival, using antibodies that specifically bind to A2E or by inducing an immune response using an A2E immunoconjugate. Enhancing survival of photoreceptor cells or decreasing accumulation of A2E in the eye using the A2E immunoconjugates or A2E specific antibodies is useful for treatment of ophthalmic diseases such as macular degeneration.

Abstract: In one aspect the present invention provides methods for assessing a physiological state of a mammalian retina in vivo, the methods of this aspect of the invention each include the steps of: (a) irradiating a portion of a mammalian retina, in vivo, with light having a wavelength in the range of from 600 nm to 1000 nm at an intensity sufficient to stimulate two-photon-induced fluorescence in the retina; and (b) assessing a physiological state of the retina by analyzing the fluorescence.

Abstract: The invention provides a transgene construct, containing a nucleic acid encoding a photoreceptor specific regulatory sequence, a membrane-associated polypeptide, and a photoreceptor outer segment targeting signal. For example, the invention pro-vides a transgene construct, containing a nucleic acid encoding a rhodopsin promoter, a membrane-associated polypeptide, and a rod outer segment (ROS) targeting signal. In addition, the invention provides a gene targeting construct containing a transgene encoding a polypeptide that contains a rod outer segment (ROS) targeting signal. The transgene is flanked by 5? and 3? DNA sequences that are homologous to the rhodopsin gene. Homologous recombination between the construct and a rhodopsin gene results in operable association between the transgene and a rod-specific regulatory sequence.

Abstract: The invention provides a transgene construct consisting of a transgene encoding a membrane polypeptide comprising a rod outer segment (ROS) targeting signal, and an operably associated species specific rod-specific regulatory sequence, wherein said polypeptide is not rhodopsin. The membrane polypeptide can be a G protein-coupled receptor (GPCR). Transgenic membrane polypeptides include a receptor selected from 5HT1A, 5HT1B, 5HT1D, 5HT1E, 5HT1F, 5HT2A, 5HT2B, 5HT2C, 5HT4A, 5HT5A, 5HT6, 5HT7A, EDG1, EDG2, EDG3, EDG4, EDG5, EDG6, EDG7, EDG8, CB2, FMLP and MC4. The invention also provides a Xenopus cell whose genome contains a transgene encoding a membrane polypeptide comprising a ROS targeting signal operably associated with a Xenopus rod-specific regulatory sequence, wherein said polypeptide is not a rhodopsin.

Abstract: The invention provides a gene targeting construct containing a transgene encoding a polypeptide that contains a rod outer segment (ROS) targeting signal. The transgene is flanked by 5′ and 3′ DNA sequences that are homologous to the rhodopsin gene. Homologous recombination between the construct and a rhodopsin gene results in operable association between the transgene and a rod-specific regulatory sequence. The invention also provides cells and animals whose genome contain a functional disruption of one or both endogenous rhodopsin gene alleles, and a transgene encoding a polypeptide that contains a ROS targeting signal operably associated with a rod-specific regulatory sequence. The invention constructs, cell and animals can be used to isolate transgenic polypeptides from the ROS membrane.

Abstract: Methods and compositions for stabilizing opsin protein in a vertebrate visual system are provided by administration of opsin-binding synthetic retinoids.

Abstract: The invention provides a gene targeting construct containing a transgene encoding a polypeptide that contains a rod outer segment (ROS) targeting signal. The transgene is flanked by 5′ and 3′ DNA sequences that are homologous to the rhodopsin gene. Homologous recombination between the construct and a rhodopsin gene results in operable association between the transgene and a rod-specific regulatory sequence. The invention also provides cells and animals whose genome contain a functional disruption of one or both endogenous rhodopsin gene alleles, and a transgene encoding a polypeptide that contains a ROS targeting signal operably associated with a rod-specific regulatory sequence. The invention constructs, cell and animals can be used to isolate transgenic polypeptides from the ROS membrane.

Abstract: The present invention discloses a three-dimensional structure of bovine rhodopsin.

Abstract: A composition useful in a method for diagnosing cancer-associated retinopathy including the steps of acquiring a purified aliquot of 26 kDa protein, and, utilizing the protein, or a unique fragment thereof, to perform a patient-serum assay to identify in a sample of a patient's serum the presence of autoantibodies to the 26 kDa protein autoantigen.

Abstract: A method of screening for cancer-associated retinopathy including the steps of acquiring a purified aliquot of 26 kDa protein, and, utilizing this protein, or peptides derived therefrom, performing a patient-serum assay to identify in a sample of a patient's serum the presence of autoantibodies to the 26 kDa protein autoantigen.