May 2004
Volume 45, Issue 13
ARVO Annual Meeting Abstract  |   May 2004
The Role of G–alphao/i Signal Transducers in Optic Nerve Development
Author Affiliations & Notes
  • V.B. Mahajan
    Jules Stein Eye Institute,
    UCLA, Los Angeles, CA
  • M. Jiang
    Molecular and Medical Pharmacology,
    UCLA, Los Angeles, CA
  • B.E. Reese
    Neuroscience Research Institute, UCSB, Santa Barbara, CA
  • D. Farber
    Jules Stein Eye Institute,
    UCLA, Los Angeles, CA
  • Footnotes
    Commercial Relationships  V.B. Mahajan, None; M. Jiang, None; B.E. Reese, None; D. Farber, None.
  • Footnotes
    Support  NIH Grant EY015141–01
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3543. doi:
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    • Get Citation

      V.B. Mahajan, M. Jiang, B.E. Reese, D. Farber; The Role of G–alphao/i Signal Transducers in Optic Nerve Development . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3543.

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

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Abstract: : Purpose: Patients with X–linked ocular albinism type 1 display macromelanosomes in the retinal pigment epithelium and misrouting of optic axons at the optic chiasm. This phenotype is due to mutations in the ocular albinism type 1 gene (OA1). Expressed by melanosomes within the retinal pigment epithelium, OA1 nucleotide sequence analysis and binding studies suggested it is a seven–transmembrane G–protein coupled receptor linked to the G–alphao/i family of signal transducers. We tested the hypothesis that G–alphao/i proteins are involved in RPE pigmentation, and whether any changes associated with the RPE phenotype yield alterations in the decussation behavior of axons at the chiasm. Methods: G–alphao/i family mouse knock out models were generated by standard methodology. After masking the genotypes, knockout mice were subjected to ophthalmologic examination, light and electron microscopy study of the RPE, and tract–tracing of the retino–fugal pathway following intravitreal injection of HRP. Results: Light and electron microscopy analysis confirmed the presence of macromelanosomes in one of the masked lines. Preliminary results from another masked line showed a mild decrease in ocular pigmentation by fundus examination. The size of the uncrossed retinofugal pathway, in this case, was reduced in both the lateral geniculate nucleus and superior colliculus relative to wild–type mice, being comparable to that found in albino mice. Conclusions: These studies suggest that the G–alphao/i family of signal transducers mediate OA1 signaling. Disruption alters melanosomal structure and/or function, yielding an albino–like decussation pattern at the optic chiasm.

Keywords: ganglion cells • neuro–ophthalmology: optic nerve • transgenics/knock–outs 

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