Authored by Sabrina Lazar - Cell Biology and Professional Writing '20
Lipids are a class of macromolecules that are usually characterized by their numerous structural carbon-hydrogen bonds and their overall hydrophobicity. Though students just learning biology may typically think of lipids as large nonpolar blobs associated with diet and fat for energy storage, these hydrocarbons also play many other essential roles. Here we examine a role of lipids in physiologic functions of the human eye and nervous system.
Polyunsaturated Fatty Acids (PUFAs) are characterized by long hydrocarbon chains, studded with double bonds and having a carboxylic acid group at one end. There are two subclasses under the PUFA umbrella: omega-3 and omega-6 fatty acids. The main distinction lies in the name; “3” and “6” denote the positions of the first double bond in the molecule, starting from the CH3 end. They are both Essential Fatty Acids (EFAs) which are are abundant and essential to the human brain and eyes, as well as in deep sea marine flora and microbes that are exposed to high pressure and low temperature conditions.
Essential fatty acids are useful for signal-transduction cascades as substrates that bind to receptors that initiate downstream cellular signals to induce the desired effect. For example, omega-3 fatty acids have been known to act as anti-inflammatory agents, but the mechanism of action was largely unexplained. New advances have proposed one pathway showing that when omega-3 fatty acids bind to GPR120, a G-protein coupled receptor, the receptor can activate subsequent pathways leading to anti-inflammatory signaling within tissues. (To read more, read the paper here).
DHA (docosahexaenoic acid) is important for visual development and retinal function. Humans cannot synthesize DHA, so it must be included in our diets. The highest DHA concentration in the human body is in the retina, the delicate membrane in the back of the eye that holds photoreceptors (rods and cones) and nerve endings. Low levels of this fatty acid in the retina has been associated with age-related macular degeneration and diabetic retinopathy.
Structure of docosahexaenoic acid (DHA)
One of DHA’s many roles in the retina is promoting photoreceptor survival and development. In rats raised on a DHA-deficient diet, photoreceptor cell cultures began to initiate apoptosis after 7-12 days, but the addition of DHA at day 7 was able to rescue the photoreceptor cells and prevented their death (Rotstein et al.). This allows time for the photoreceptors to develop and undergo apical membrane differentiation, which elongates the cell.
In neuronal tissue, DHA is involved in neurotransmitter carrier-mediated transport between synapses. One example takes place where the axon terminal converges onto the target cell. Since most neurotransmitters leave the neuron encased in vesicles, they must first travel, bind, and fuse to the correct target membrane. This specificity is mediated through proteins called SNAREs; the incoming vesicle has v-SNAREs, and the target membrane holds t-SNAREs, which entwine upon vesicle docking. DHA has been found to facilitate formation of this SNARE complex, which facilitates the fusion of neurotransmitter-carrying synaptic vesicles to the target cell. In this way, DHA plays an essential role in neuronal signaling. Read a review of DHA functions here.
“Essential Fatty Acids”. American Optometric Association. https://www.aoa.org/patients-and-public/caring-for-your-vision/diet-and-nutrition/essential-fatty-acids
“Office of Dietary Supplements - Omega-3 Fatty Acids.” NIH Office of Dietary Supplements, U.S. Department of Health and Human Services, 21 Nov. 2018, ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/.
“Rhodopsin” Encyclopedia Britannica. https://www.britannica.com/science/rhodopsin
“GPCR” - Nature Education. https://www.nature.com/scitable/topicpage/gpcr-14047471
GPR120 Oh et al. Oh, Da Young, et al. "GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects." Cell 142.5 (2010): 687-698.
“Apoptosis” - Khan Academy. https://www.khanacademy.org/science/biology/developmental-biology/apoptosis-in-development/a/apoptosis
Photoreceptor survival: Rotstein, Nora P., et al. "Docosahexaenoic acid is required for the survival of rat retinal photoreceptors in vitro." Journal of neurochemistry 66.5 (1996): 1851-1859.
“Apical” - Dictionary.com https://www.dictionary.com/browse/apical
“SNAREs” - ScienceDirect. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/snare-protein
DHA function review : Tanaka, Kazuhiro, et al. "Effects of docosahexaenoic acid on neurotransmission." Biomolecules & therapeutics 20.2 (2012): 152.