The long term goal is to understand the molecular genetics of vision that is based on cone photopigments.
Specific aim 1 will determine the relationship between cone photopigment genes on the X-chromosome and those transcribed in the retina. A comparison of the genomic cone photopigment genes with the presence of photopigment messenger RNA in the human retina will provide a basis for understanding what determines which photopigment genes are """"""""turned on"""""""" and what controls the level at which each gene is expressed.
Specific aim 2 will characterize how the cone populations and the pigment mRNAs vary within an eye at different retinal locations and how they vary across individuals. These are essential steps toward understanding the mechanisms that govern the decision of an undifferentiated cell to become an L-cone or an M-cone.
Specific aim 3 will test the hypothesis that normal polymorphic amino acids occur in abnormal combinations in cone-based vision disorders and will explore whether such abnormalities cause the disorders. The pigment genes contain scattered nucleotide polymorphisms. These specify several normal amino acid substitutions that occur in varied combinations among the pigments. Individually, each amino acid substitution is benign. However, specific mRNAs which would specify particular combinations of amino acids have not been detected in human retinas. However, genes that would specify those combinations appear to occur with high frequency in cone-based vision disorders. This suggests that, in these disorders, the pigment may contain particular amino acid combinations which are unstable and adversely affect cone function or viability.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences C Study Section (VISC)
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Mariani, Andrew P
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Medical College of Wisconsin
Anatomy/Cell Biology
Schools of Medicine
United States
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Greenwald, Scott H; Kuchenbecker, James A; Rowlan, Jessica S et al. (2017) Role of a Dual Splicing and Amino Acid Code in Myopia, Cone Dysfunction and Cone Dystrophy Associated with L/M Opsin Interchange Mutations. Transl Vis Sci Technol 6:2
Davidoff, Candice; Neitz, Maureen; Neitz, Jay (2016) Genetic Testing as a New Standard for Clinical Diagnosis of Color Vision Deficiencies. Transl Vis Sci Technol 5:2
Neitz, Maureen; Neitz, Jay (2014) Curing color blindness--mice and nonhuman primates. Cold Spring Harb Perspect Med 4:a017418
Greenwald, Scott H; Kuchenbecker, James A; Roberson, Daniel K et al. (2014) S-opsin knockout mice with the endogenous M-opsin gene replaced by an L-opsin variant. Vis Neurosci 31:25-37
McClements, Michelle; Davies, Wayne I L; Michaelides, Michel et al. (2013) Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy. Invest Ophthalmol Vis Sci 54:1361-9
McClements, Michelle; Davies, Wayne I L; Michaelides, Michel et al. (2013) X-linked cone dystrophy and colour vision deficiency arising from a missense mutation in a hybrid L/M cone opsin gene. Vision Res 80:41-50
Carroll, Joseph; Dubra, Alfredo; Gardner, Jessica C et al. (2012) The effect of cone opsin mutations on retinal structure and the integrity of the photoreceptor mosaic. Invest Ophthalmol Vis Sci 53:8006-15
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Neitz, Jay; Neitz, Maureen (2011) The genetics of normal and defective color vision. Vision Res 51:633-51
Carroll, Joseph; Rossi, Ethan A; Porter, Jason et al. (2010) Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaic. Vision Res 50:1989-99

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