May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Cone Photoreceptor Viability in the Absence of Rds Protein
Author Affiliations & Notes
  • R. Farjo
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • J. Skaggs
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • Z. Nash
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • A.B. Quiambao
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • G. Moiseyev
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • B.A. Nagel
    Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO
  • X.–Q. Ding
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • J.–X. Ma
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • S.J. Fliesler
    Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO
  • M.I. Naash
    Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • Footnotes
    Commercial Relationships  R. Farjo, None; J. Skaggs, None; Z. Nash, None; A.B. Quiambao, None; G. Moiseyev, None; B.A. Nagel, None; X. Ding, None; J. Ma, None; S.J. Fliesler, None; M.I. Naash, None.
  • Footnotes
    Support  NIH EY10609 (MIN), EY12190 (MIN), EY07361 (SJF), and RPB (SJF)
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 5186. doi:
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      R. Farjo, J. Skaggs, Z. Nash, A.B. Quiambao, G. Moiseyev, B.A. Nagel, X.–Q. Ding, J.–X. Ma, S.J. Fliesler, M.I. Naash; Cone Photoreceptor Viability in the Absence of Rds Protein . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5186.

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

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Abstract

Abstract: : Purpose: To assess the role of the Retinal Degeneration Slow (Rds) protein in the cone–dominated retina of Neural Retina Leucine Zipper (Nrl)–deficient mice. Methods: We generated a double knockout mouse lacking both Nrl and Rds (Nrl–/–/Rds–/–). Quantitative RT–PCR and Western Blot analysis were used to examine expression levels of genes involved in phototransduction and maintenance of outer segment (OS) structure. Retinal function was assessed with electroretinography (ERG) at postnatal (P) days 30, 60, and 90. The presence and levels of the visual chromophore, 11–cis retinal, were assessed by HPLC. Retinal histology was examined, and immunohistochemistry was used to localize retina–specific proteins. Correlative ultrastructural (EM) and immunogold analyses were also performed. Results: Expression levels of phototransduction genes in the Nrl–/–/Rds–/– retina mimicked those observed in the Nrl–/–. At P30, photopic b–wave amplitudes were: wild–type, 245 µV; Nrl–/–, 730 µV; Rds–/–, 0 µV; and Nrl–/–/Rds–/–, 385 µV. Unlike the Nrl–/– mice, cone ERG signal was maintained in the Nrl–/–/Rds–/– through P90. HPLC analysis demonstrated the presence of 11–cis retinal in Nrl–/–/Rds–/– retinas. Morphological analysis of Nrl–/–/Rds–/– retinas revealed a similar cytological organization as observed in Nrl–/– mice, but with significantly fewer rosettes and retinal folds and with dysmorphic remnant photoreceptors. Retinal immunohistochemistry of Nrl–/–/Rds–/– mice with antibodies against S–opsin and other OS proteins exhibited labeling of tubular–like structures in the subretinal space, in marked contrast to the compact labeling of discs observed in the cone OS of Nrl–/– mice. EM of Nrl–/–/Rds–/– retinas further demonstrated the presence of aberrant membranous structures in the subretinal space and remnant photoreceptor layer, rather than characteristic cone OS structures. Conclusions: The loss of Rds in the cone–dominated retina of the Nrl–/– mouse produces viable, yet morphologically abnormal, photoreceptors capable of phototransduction. As compared to the Rds–/– mouse, these data demonstrate an inherent differential response of rod and cone photoreceptors to the ablation of Rds. This work further establishes the predicted role of the Rds protein in cone OS formation, as its absence causes defective disc morphogenesis.

Keywords: photoreceptors • microscopy: light/fluorescence/immunohistochemistry • retinal development 
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