April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
The Loss of vacuolar protein sorting 11 (vps11) Causes Retinal Pathogenesis in a Vertebrate Model of Syndromic Albinism
Author Affiliations & Notes
  • Ryan Thummel
    Anatomy & Cell Biology and Ophthalmology,
    Wayne State University School of Medicine, Detroit, Michigan
  • Jennifer L. Thomas
    Anatomy & Cell Biology,
    Wayne State University School of Medicine, Detroit, Michigan
  • Thomas S. Vihtelic
    Experimental Therapeutics, MPI Research, Inc, Mattawan, Michigan
  • Ronald G. Gregg
    Biochem & Molecular Biology, University of Louisville, Louisville, Kentucky
  • David R. Hyde
    Dept of Biological Sciences, University of Notre Dame, Notre Dame, Indiana
  • Footnotes
    Commercial Relationships  Ryan Thummel, None; Jennifer L. Thomas, None; Thomas S. Vihtelic, None; Ronald G. Gregg, None; David R. Hyde, None
  • Footnotes
    Support  R21EY019401, R21EY018919
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1825. doi:
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    • Get Citation

      Ryan Thummel, Jennifer L. Thomas, Thomas S. Vihtelic, Ronald G. Gregg, David R. Hyde; The Loss of vacuolar protein sorting 11 (vps11) Causes Retinal Pathogenesis in a Vertebrate Model of Syndromic Albinism. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1825.

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

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Abstract

Purpose: : To establish the zebrafish platinum mutant as a model for studying vision defects caused by syndromic albinism diseases such as Chediak-Higashi syndrome, Griscelli syndrome, and Hermansky-Pudlak syndrome (HPS).

Methods: : Bulked segregant analysis and candidate gene sequencing revealed that the zebrafish platinum mutation is a single nucleotide insertion in the vps11 (vacuolar protein sorting 11) gene. Expression of vps11 was determined by RT-PCR and in situ hybridization. Mutants were analyzed for pigmentation defects and retinal pathology by histology, immunohistochemistry, and transmission electron microscopy.

Results: : Phenocopy and rescue experiments determined that a loss of Vps11 results in the platinum phenotype. Expression of vps11 appeared ubiquitous during zebrafish development, with stronger expression in the developing retina and retinal pigmented epithelium (RPE). Zebrafish platinum mutants exhibited reduced pigmentation in the body and retinal pigmented epithelium (RPE), however, melanophore development, migration, and dispersion occurred normally. RPE, photoreceptors, and inner retinal neurons formed normally in zebrafish platinum mutants. However, a gradual loss of RPE, an absence of mature melanosomes and the subsequent degradation of RPE/photoreceptor interdigitation was observed.

Conclusions: : These data show that Vps11 is not required for normal retinal development or initiation of melanin biosynthesis, but is required for melanosome maturation and healthy maintenance of the RPE and photoreceptors.

Keywords: retinal degenerations: cell biology • retinal pigment epithelium • proteins encoded by disease genes 
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