May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Involvement of OA1, an Intracellular GPCR, and Gi3, Its Binding Protein, in Melanosomal Biogenesis and Optic Pathway Formation
Author Affiliations & Notes
  • A. Young
    UCLA-Jules Stein Eye Institute, Los Angeles, California
  • E. B. Powelson
    UCSB, Santa Barbara, California
  • I. E. Whitney
    UCSB, Santa Barbara, California
  • M. A. Raven
    UCSB, Santa Barbara, California
  • M. Jiang
    Molecular and Medical Pharmacology, UCLA, Los Angeles, California
  • S. Nusinowitz
    UCLA-Jules Stein Eye Institute, Los Angeles, California
  • B. E. Reese
    UCSB, Santa Barbara, California
  • D. B. Farber
    UCLA-Jules Stein Eye Institute, Los Angeles, California
  • Footnotes
    Commercial Relationships  A. Young, None; E.B. Powelson, None; I.E. Whitney, None; M.A. Raven, None; M. Jiang, None; S. Nusinowitz, None; B.E. Reese, None; D.B. Farber, None.
  • Footnotes
    Support  NIH Grant EY015141 and The Vision of Children Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 785. doi:
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      A. Young, E. B. Powelson, I. E. Whitney, M. A. Raven, M. Jiang, S. Nusinowitz, B. E. Reese, D. B. Farber; Involvement of OA1, an Intracellular GPCR, and Gi3, Its Binding Protein, in Melanosomal Biogenesis and Optic Pathway Formation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):785. doi:

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Ocular albinism type 1 (OA1) is an X-linked recessive disease characterized by hypopigmentation of the RPE, abnormal crossing of the optic axons, nystagmus, strabismus, foveal hypoplasia, and reduced visual acuity. The OA1 gene encodes a G-protein coupled receptor that co-immunoprecipitates with the Gαi subunit of heterotrimeric G proteins from human melanocyte extracts. Taking advantage of the availability of Gαi3 knockout mice, we investigated whether Gαi3 is involved in the transduction pathway controlled by OA1. Our hypothesis is that if Gαi3 and OA1 proteins signal in the same pathway, the RPE phenotype should be very similar, as should be the downstream consequences for the chiasmatic phenotype.

Methods: : We compared 3-month-old Oa1 and Gαi3 knockout mice and their corresponding controls (129Sv and B6/Ncrl, respectively) by: 1) light and electron microscopy, to study the photoreceptors and RPE melanosomes phenotype, 2) retrograde labeling with HRP, to investigate the size of the uncrossed retinofugal pathway, and 3) electroretinography (ERG), to analyze the retinal physiology.

Results: : Light and electron microscopy showed that Gαi3-/- and Oa1-/- photoreceptors were comparable to those of corresponding wild-type retinas. Morphometrical analysis indicated that the average melanosomal density of Gαi3-/- and Oa1-/- RPEs was significantly different from that of the control RPEs. In addition, the RPE cells of Gαi3-/- and Oa1-/- mice showed macromelasomes: those from Gαi3-/- mice were two times the size of the 129Sv-normal melanosomes, and those from Oa1-/- mice were three times the size of B6/Ncrl RPE melanosomes. Even though there were no differences in ERG parameters between Gαi3-/-, Oa1-/- and their control mice, retrograde labeling with HRP showed that there was a significant reduction in the size of the ipsilateral retinofugal projections in Oa1 and Gαi3 knock-out mice.

Keywords: retinal pigment epithelium • transgenics/knock-outs • ganglion cells 

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