Introduction to the Thematic Review Series: Seeing 2020: lipids and lipid-soluble molecules in the eye

The emerging roles of the macular pigment carotenoids throughout the lifespan and in prenatal supplementationJournal of Lipid ResearchVol. 62PreviewSince the publication of the Age-Related Eye Disease Study 2 (AREDS2) in 2013, the macular pigment carotenoids lutein (L) and zeaxanthin (Z) have become well known to both the eye care community and the public. It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration. Full-Text PDF Open AccessFatty acid oxidation and photoreceptor metabolic needsJournal of Lipid ResearchVol. 62PreviewPhotoreceptors have high energy demands and a high density of mitochondria that produce ATP through oxidative phosphorylation (OXPHOS) of fuel substrates. Although glucose is the major fuel for CNS brain neurons, in photoreceptors (also CNS), most glucose is not metabolized through OXPHOS but is instead metabolized into lactate by aerobic glycolysis. The major fuel sources for photoreceptor mitochondria remained unclear for almost six decades. Similar to other tissues (like heart and skeletal muscle) with high metabolic rates, photoreceptors were recently found to metabolize fatty acids (palmitate) through OXPHOS. Full-Text PDF Open AccessSignaling roles of phosphoinositides in the retinaJournal of Lipid ResearchVol. 62PreviewThe field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (also known as phosphatidylinositol phosphates or PIPs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of phosphoinositide kinases and phosphoinositide phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule, phosphatidylinositol. Full-Text PDF Open AccessLipid metabolism dysregulation in diabetic retinopathyJournal of Lipid ResearchVol. 62PreviewLipid metabolic abnormalities have emerged as potential risk factors for the development and progression of diabetic complications, including diabetic retinopathy (DR). This review article provides an overview of the results of clinical trials evaluating the potential benefits of lipid-lowering drugs, such as fibrates, omega-3 fatty acids, and statins, for the prevention and treatment of DR. Although several clinical trials demonstrated that treatment with fibrates leads to improvement of DR, there is a dissociation between the protective effects of fibrates in the retina, and the intended blood lipid classes, including plasma triglycerides, total cholesterol, or HDL:LDL cholesterol ratio. Full-Text PDF Open AccessDocosanoid signaling modulates corneal nerve regeneration: effect on tear secretion, wound healing, and neuropathic painJournal of Lipid ResearchVol. 62PreviewThe cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as prolonged use of contact lenses and surgeries to correct vision can produce nerve damage. There are no effective therapies to alleviate DED (a multifunctional disease) and several clinical trials using ω-3 supplementation show unclear and sometimes negative results. Full-Text PDF Open AccessLipid conformational order and the etiology of cataract and dry eyeJournal of Lipid ResearchVol. 62PreviewLens and tear film lipids are as unique as the systems they reside in. The major lipid of the human lens is dihydrosphingomylein, found in quantity only in the lens. The lens contains a cholesterol to phospholipid molar ratio as high as 10:1, more than anywhere else in the body. Lens lipids contribute to maintaining lens clarity, and alterations in lens lipid composition due to age are likely to contribute to cataract. Lens lipid composition reflects adaptations to the unique characteristics of the lens: no turnover of lens lipids or proteins; the lowest amount of oxygen of any tissue; and contains almost no intracellular organelles. Full-Text PDF Open AccessRetinoids in the visual cycle: role of the retinal G protein-coupled receptorJournal of Lipid ResearchVol. 62PreviewDriven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11-cis-retinal to the all-trans configuration. This photochemical reaction initiates the signal transduction pathway that eventually leads to the transmission of a visual signal to the brain and leaves the opsins insensitive to further light stimulation. For the eye to restore light sensitivity, opsins require recharging with 11-cis-retinal. This trans-cis back conversion is achieved through a series of enzymatic reactions composing the retinoid (visual) cycle. Full-Text PDF Open AccessBisretinoid phospholipid and vitamin A aldehyde: shining a lightJournal of Lipid ResearchVol. 62PreviewVitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor cell outer segments. Following absorption of a photon, the 11-cis-retinal chromophore of visual pigment in photoreceptor cells isomerizes to all-trans-retinal. To maintain photosensitivity 11-cis-retinal must be replaced. At the same time, however, all-trans-retinal has to be handled so as to prevent nonspecific aldehyde activity. Full-Text PDF Open AccessVery long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4Journal of Lipid ResearchVol. 62PreviewLipids play essential roles in maintaining cell structure and function by modulating membrane fluidity and cell signaling. The fatty acid elongase-4 (ELOVL4) protein, expressed in retina, brain, Meibomian glands, skin, testes and sperm, is an essential enzyme that mediates tissue-specific biosynthesis of both VLC-PUFA and VLC-saturated fatty acids (VLC-SFA). These fatty acids play critical roles in maintaining retina and brain function, neuroprotection, skin permeability barrier maintenance, and sperm function, among other important cellular processes. Full-Text PDF Open AccessSphingolipids as critical players in retinal physiology and pathologyJournal of Lipid ResearchVol. 62PreviewSphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is therefore crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Full-Text PDF Open Access In 2010, this journal published a series of review articles in a Thematic Issue entitled “Lipids and Lipid Metabolism in the Eye.” Over the ensuing decade, a number of significant advances have been made that are pertinent to this broad topic, which prompted us to launch a follow-up Thematic Issue to present updates on several of the topics reviewed in that prior issue as well as to expand into new areas that previously had not been addressed. In addition to considering the conventional classes of lipids (e.g., glycerophospholipids, sphingolipids, fatty acids, and sterols), we also wanted to address some key lipid-soluble molecules (e.g., retinoids, bisretinoids, and carotenoids) that play important physiological roles in ocular tissues. Given that this issue concerns the eye (where normal visual acuity is referred to as “20/20” vision) as well as the fact that we have just emerged from the year 2020, we have purposely employed a bit of double-entendre in naming this Thematic Issue “Seeing 2020: lipids and lipid-soluble molecules in the eye.” Below, we present a brief overview of each of the articles included in this Thematic Issue, proceeding anatomically from the back to the front of the eye. While the majority of these articles concern various aspects of lipid biochemistry and eye diseases pertinent to the retina, we’ve also included articles germane to the lens and cornea (Fig. 1). Retinoids comprise a diverse family of organic compounds derived from vitamin A that play a central role in the physiology of the retina. Most notably, the 11-cis isomer of vitamin A aldehyde (11-cis retinaldehyde) serves as the chromophore covalently linked to proteins (rod and cone opsins) to generate the visual pigments of rod and cone photoreceptor cells. The “visual cycle” involves a series of events, including conversion of vitamin A alcohol (all-trans retinol) to 11-cis retinaldehyde, delivery of that retinoid to the photoreceptors to generate rhodopsin (the rod-specific visual pigment) and the cone visual pigments, and conversion of the all-trans retinal hydrolyzed from the visual pigment protein upon absorption of light (thus initiating the visual phototransduction process) back to 11-cis retinaldehyde. In vertebrates, this also entails several other steps as well as a series of enzymes, binding partners, and transport proteins; the latter are required to shuttle the lipid-soluble retinoids through the aqueous extracellular environment. The neighboring retinal pigment epithelium (RPE) as well as Müller glial cells in the neural retina play parallel roles in this cycle, regenerating 11-cis retinal and supplying it to rods and cones, respectively. Choi et al. (1Choi E.H. Daruwalla A. Suh S.

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