May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
The U4/U6.U5 Tri-Small Nuclear Riboprotein Complex Involved in Four Forms of Autosomal Dominant Retinitis Pigmentosa May Be Hypoxia-Regulated
R. G. Schmidt-Kastner; H. Yamamoto; D. Hamasaki; H. Yamamoto; J.-M. Parel; C. Schmitz; J. Blanks; M. Preising
Author Affiliations & Notes
  • R. G. Schmidt-Kastner
    College of Biomedical Science, Florida Atlantic University, Boca Raton, Florida
  • H. Yamamoto
    Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, Univ. Miami Miller School of Medicine, Miami, Florida
  • D. Hamasaki
    Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, Univ. Miami Miller School of Medicine, Miami, Florida
  • H. Yamamoto
    Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, Univ. Miami Miller School of Medicine, Miami, Florida
  • J.-M. Parel
    Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, Univ. Miami Miller School of Medicine, Miami, Florida
  • C. Schmitz
    Dept. of Neuroscience, Maastricht University, Maastricht, The Netherlands
  • J. Blanks
    College of Biomedical Science, Florida Atlantic University, Boca Raton, Florida
  • M. Preising
    Dept. of Pediatric Ophthalmology, Strabismology and Ophthalmogenetics, Regensburg University Medical Center, Regensburg, Germany
  • Footnotes
    Commercial Relationships R.G. Schmidt-Kastner, None; H. Yamamoto, None; D. Hamasaki, None; H. Yamamoto, None; J. Parel, None; C. Schmitz, None; J. Blanks, None; M. Preising, None.
  • Footnotes
    Support Florida Lions Eye Bank; NIH center grant P30-EY014801; Corneal SA, Paris, France; Research to Prevent Blindness; Henri and Flore Lesieur Foundation; DFG Lo457/5-1-2.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3713. doi:
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      R. G. Schmidt-Kastner, H. Yamamoto, D. Hamasaki, H. Yamamoto, J.-M. Parel, C. Schmitz, J. Blanks, M. Preising; The U4/U6.U5 Tri-Small Nuclear Riboprotein Complex Involved in Four Forms of Autosomal Dominant Retinitis Pigmentosa May Be Hypoxia-Regulated. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3713.

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Abstract

Purpose:: High oxygen consumption and cyclical changes of oxygen levels related to dark-adaptation are critical for the normal function of photoreceptors. Changes in oxygenation may explain the selective vulnerability in retinitis pigmentosa (RP) for those forms involving genes with global cellular functions. Assuming similarity between the retina and brain, data mining of ischemia-hypoxia response (IHR) genes of the brain should identify oxygen regulated genes in protein complexes related to RP genes. The U4/U6.U5 tri small nuclear ribonucleoprotein (tri-snRNP) complex of the spliceosome was targeted for analysis, because mutations in four globally expressed genes cause RP (RP9 (PAP1), RP11 (PRPF31), RP13 (PRPF8), and RP18 (PRPF3)).

Methods:: A database of IHR genes was generated from expression profiling studies in the rodent brain (n=24). Genes related to human retinal degeneration were extracted first using OMIM. The database was then examined for regulated genes of the U4/U6.U5 tri-snRNP complex, and retinal expression was ascertained (NEIBank). Immunohistochemistry localized one protein in the cynomolgus monkey (n=3) or human retina (n=1).

Results:: Three IHR genes were directly linked to retinal degeneration (CNGB1, SEMA4A, RRG4) and one indirectly through Pim1, the binding partner of PAP (RP9). Three IHR genes contributed to the U4/U6.U5 tri-snRNP complex, viz. a) PRPF4; b) SART1 / 110 kDa SR-related protein of the U4/U6.U5 tri-snRNP / hypoxia associated factor (HAF); and c) LSM8. The 110 kDa SR-related protein was expressed in photoreceptors.

Conclusions:: Regulation by changes in oxygenation within the U4/U6.U5 tri-snRP complex could be particularly important for photoreceptors, because oxygen consumption follows a circadian rhythm. If the complex is impaired by mutations in any of the four genes causing RP, it may be unable to follow the physiological demands of oxygenation mediated by the three genes identified here by data mining.

Keywords: retinitis • hypoxia • genetics 
© 2007, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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