Our lab is focused on studies of retinal degenerations caused by metabolic defects, particularly dyslipidemias involving defective cholesterol metabolism (e.g., Smith-Lemli-Opitz syndrome), using pharmacological and transgenic animal models. Current studies are focused on the role of lipid and protein oxidation in the underlying mechanisms of photoreceptor cell death in such retinal degenerations, using a combination of genomic, proteomic, and lipidomic approaches. We also are studying how allelic apoE isoforms may modulate the severity and duration of retinal degenerations, using transgenic mice that express either human apoE3 or human apoE4 superimposed on an established transgenic mouse model of progressive retinal degeneration. Our lab has established multiple collaborations with vision scientists at other institutions, both domestically and abroad, to pursue these studies, as well as others that involve fundamental aspects of retinal cell biology and biochemistry with relevance to human hereditary retinal degenerations, and gene therapy. In recent years, this work has been supported by individual grants from the NEI/NIH (RO1 EY007361; R21 EY017019), the March of Dimes, the Foundation Fighting Blindness (FFB), and both a Senior Scientific Investigator Award as well as an unrestricted departmental grant from Research to Prevent Blindness (RPB)

1. Fliesler SJ, Peachey NS, Richards MJ, Nagel BA, and Vaughan DK. Retinal degeneration in a rodent model of Smith-Lemli-Opitz syndrome: Electrophysiological, biochemical, and morphological features. Arch. Ophthalmol. 2004; 122: 1190-1200.
2. Fliesler SJ, Vaughan DK, Jenewein EC, Richards MJ, Nagel BA, Peachey NS. Partial rescue of retinal function and sterol steady-state in a rat model of Smith-Lemli-Opitz syndrome. Pediatr. Res. 2007; 61: 273-278.
3. Ford DA, Richards MJ, Brush RS, Anderson RE, and Fliesler SJ. Lipidomic analysis of the retina in a rat model of Smith-Lemli-Opitz syndrome: Alterations in docosahexaenoic acid content of phospholipid molecular species. J. Neurochem, 2008; 105: 1032-1047.
4. Rodriguez IR and Fliesler SJ. Photo-damage generates 7-keto- and 7-hydroxycholesterol in the rat retina via a free radical-mediated mechanism. Photochem. Photobiol. 2009; 85: 1116-1125.
5. Fliesler SJ and Bretillon L. The ins and outs of cholesterol in the vertebrate retina. J. Lipid Res. 2010; 51: 3399-3413.
6. Fliesler SJ. Retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome: thinking beyond cholesterol deficiency. Adv. Exp. Med. Biol. 2010; 664: 481-489.
7. Xu L, Liu W, Sheflin LG, Fliesler SJ, Porter NA. Novel oxysterols observed in tissues and fluids of AY9944-treated rats: a model for Smith-Lemli-Opitz syndrome. J. Lipid Res. 2011; 52: 1810-1820.