Smith-Lemli-Opitz Syndrome (SLOS) is a recessive hereditary disease caused by an enzymatic defect in the biosynthesis of cholesterol. To date, the therapeutic standard of care for this disease has been cholesterol supplementation therapy. However, the efficacy of this treatment is extremely variable and, in many if not most cases, is poor. Results of studies using animal models of SLOS have suggested that cholesterol deficiencyand/or the aberrant accumulation of the immediate precursor of cholesterol (7-dehydrocholesterol (7DHC)), per se, may not be the sole culprits in the pathobiology of this disease. Rather, cytotoxic oxysterol by-products derived specifically from 7DHC are thought to be additional, significant, causative players in the disease mechanism. Based in large measure upon such studies, a recent clinical trial, comparing the therapeutic efficacyof cholesterol supplementation alone vs. combined cholesterol-antioxidant supplementation in SLOS patients, has provided extremely encouraging results that tend to both validate the proposed role of oxysterols in the pathobiology of SLOS as well as indicate an improved treatment for this and related diseases.

The vertebrate eye is a complex sensory organ consisting of multiple, distinct tissues, each having its own unique biochemical composition, structure, and physiological function. Key among these are the retina, lens, and cornea, working in concert to bring photons of light into the eye, focus them correctly on the retina, and convert their energy into electrochemical signals that are conveyed to the brain where, ultimately, they are processed into a coherent visual image. Defects in any or all of these tissues, whether inborn or acquired, whether through a disease process or by traumatic injury, can compromise vision and, eventually, may result in complete and irreversible blindness.The study of lipids and lipid metabolism in relation to ocular tissues has not been reviewed heretofore in any single text or organized collection of monographs or review articles. Such discussions are usually relegated to a relatively small subsection of a review article or text that more broadly addresses the biochemistry of the eye or one of its constituent tissues. Yet, lipids and lipid-soluble compounds are essential constituents of the cells and tissues that comprise the eye, and defects in their synthesis, intracellular and extracellular transport, and turnover underlie a variety of signifi cant, common, and often severely debilitating eye diseases. Classical " grind and fi nd " lipid composition analyses have given way more recently to detailed lipidomic, metabolomic, and lipid-dependent signaling studies, linking a detailed, quantitative knowledge of lipids and bioactive, lipid-derived molecules to a more comprehensive understanding of the structure, function, and pathophysiology of ocular tissues. Starting in January 2010, a series of 11 monthly review articles will appear in the Journal of Lipid Research that will provide an overview of topics relevant to lipids and lipid metabolism in the retina, lens, and cornea of the vertebrate eye.The retina is a complex neurosensory tissue comprised of at least six neuronal cell types that are organized into distinct cell layers, in addition to glia (e.g., Müller cells) and astrocytes. It is nourished by two distinct blood supplies, the choroid and the inner retinal vasculature. Historically, much of what we know about lipids and lipid metabolism in the retina has been obtained within the context of studies that have addressed membrane assembly and turnover in the rod and (to a lesser extent) cone photoreceptor cells. However, more recently, studies of lipids and lipid metabolism in the retina have focused on disease processes caused by either an over-abundance or, in some instances, a defi ciency of specifi c lipid species within retinal cells or their surrounding extracellular environment, often resulting in toxic insult to these cells and ensuing retinal dysfunction, cell death, and progressive retinal degeneration. The majority of this thematic series will address topics pertinent to lipid composition and metabolism and lipid-mediated signaling in the retina.Dr. Raju Rajala will ...

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