May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Lipidomic Analysis of Retinas From Control and AY9944–Treated Rats: A Model of Smith–Lemli–Opitz Syndrome
Author Affiliations & Notes
  • M.J. Richards
    Ophthalmology and Pharmacol. & Physiol. Sci, Saint Louis Univ Eye Inst, St Louis, MO
  • D.A. Ford
    Biochemistry & Molec. Biol., Saint Louis Univ. Scholl of Medicine, St Louis, MO
  • S.J. Fliesler
    Ophthalmology and Pharmacol. & Physiol. Sci, Saint Louis Univ Eye Inst, St Louis, MO
  • Footnotes
    Commercial Relationships  M.J. Richards, None; D.A. Ford, None; S.J. Fliesler, None.
  • Footnotes
    Support  : EY07361 (SJF), HL42665 (DAF), RR019232 (DAF), and RPB (SJF)
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3196. doi:
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      M.J. Richards, D.A. Ford, S.J. Fliesler; Lipidomic Analysis of Retinas From Control and AY9944–Treated Rats: A Model of Smith–Lemli–Opitz Syndrome . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3196.

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

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Abstract

Abstract: : Purpose: Treatment of Sprague Dawley rats with AY9944, an inhibitor of dehydrosterol–Δ7– reductase, produces an animal model of Smith–Lemli–Opitz Syndrome (SLOS), including grossly elevated 7–dehydrocholesterol (7DHC) and diminished cholesterol (Chol) levels in all tissues and progressive retinal degeneration (Fliesler et al., Arch. Ophthalmol. 122:1190, 2004). Here, we examined concomitant changes in the lipidome of retinas from the SLOS rat model, in comparison with age–matched controls. Methods: Sprague Dawley rats were treated with AY9944 as previously described (Fliesler et al., 2004) for 11 wk; control litters (age– and sex–matched) received no drug. All animals were maintained under dim cyclic light (12L:12D, 20–40 lux) and fed a cholesterol–free diet and water ad lib. Total lipids were extracted from individual retinas per the Bligh & Dyer method (Can. J. Biochem. 37:911, 1959), including an internal standard of di–C20:0–phosphatidylcholine (PC), and the organic (CHCl3) layer was subjected to direct quadrupole mass spectrometric analysis (TSQ Quantum Ultra), in both positive and negative ion modes. Companion retinas were directly saponified, and the extracted (petroleum ether) nonsaponifiable lipids were analyzed for sterol composition by HPLC. Results: Retinas from AY9944–treated rats had 7DHC/Chol mole ratios of 5.60 ± 1.36, whereas in control retinas the ratio was zero; total Chol content (nmoles/retina) of SLOS rat retinas was 9.20 ± 2.53, compared to 67.83 ± 3.70 in controls. The patterns of PC and phosphatidylethanolamine (PE) molecular species were grossly different, comparing SLOS rat retinas vs. controls. Notably, there were marked decreases in C18:0/C22:6–diacyl–PC and –PE, and di–C16:0–diacyl–PC in SLOS rat retinas, vs. controls. Conclusions: The retinal lipidome, as represented by PC and PE molecular species, is globally altered in the SLOS rat model, relative to control rats. These findings suggest cross–talk between the sterol pathway and other lipid pathways, implicating additional metabolic compromise beyond the primary enzymatic defect in the etiology of SLOS.

Keywords: lipids • retinal degenerations: cell biology • oxidation/oxidative or free radical damage 
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