HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: iovs.08-3190v1 50/7/3074    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Grossman, G. H. Articles by Hagstrom, S. A. Search for Related Content PubMed PubMed Citation Articles by Grossman, G. H. Articles by Hagstrom, S. A.

Early Synaptic Defects in tulp1^–/– Mice

¹From the Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; ²Research Service, Cleveland Veterans Administration Medical Center, Cleveland, Ohio; and ³Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio.

PURPOSE. Mutations in the photoreceptor-specific tubby-like protein 1 (TULP1) underlie a form of autosomal recessive retinitis pigmentosa. To investigate the role of Tulp1 in the photoreceptor synapse, the authors examined the presynaptic and postsynaptic architecture and retinal function in tulp1^–/– mice

METHODS. The authors used immunohistochemistry to examine tulp1^–/– mice before retinal degeneration and made comparisons with wild-type (wt) littermates and retinal degeneration 10 (rd10) mice, another model of photoreceptor degeneration that has a comparable rate of degeneration. Retinal function was characterized with the use of electroretinography.

RESULTS. In wt mice, Tulp1 is localized to the photoreceptor synapse. In the tulp1^–/– synapse, the spatial relationship between the ribbon-associated proteins Bassoon and Piccolo are disrupted, and few intact ribbons are present. Furthermore, bipolar cell dendrites are stunted. Comparable abnormalities are not seen in rd10 mice. The leading edge of the a-wave had normal kinetics in tulp1^–/– mice but reduced gain in rd10 mice. The b-wave intensity-response functions of tulp1^–/– mice are shifted to higher intensities than in wt mice, but those of rd10 mice are not.

CONCLUSIONS. Photoreceptor synapses and bipolar cell dendrites in tulp1^–/– mice display abnormal structure and function. A malformation of the photoreceptor synaptic ribbon is likely the cause of the dystrophy in bipolar cell dendrites. The association of early-onset, severe photoreceptor degeneration preceded by synaptic abnormalities appears to represent a phenotype not previously described. Not only is Tulp1 critical for photoreceptor function and survival, it is essential for the proper development of the photoreceptor synapse.