Elovl2 Is Required for Robust Visual Function in Zebrafish

Abstract

Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) play critical roles in membrane stability and cell signaling within the retina. ELOVL2 (Elongation of Very Long Chain Fatty Acids-Like 2), an elongase involved in the synthesis of long chain polyunsaturated fatty acids (LC-PUFAs), has recently been implicated in regulating aging in the mammalian retina. In this work, we characterize the expression and function of elovl2 in the retina development in embryonic zebrafish. Whole mount in situ hybridization shows elovl2 is expressed in the Muller glia in embryonic and adult zebrafish. Lipidomics analysis of elovl2 crispants whole embryos at day 2 and eyes at day 7 demonstrated significant changes in lipids composition, especially on the level of lipids containing docosahexaenoic acid (DHA). Histological analysis of zebrafish lacking elovl2 revealed increased retinal thickness compared to controls at day 7 without gross disruptions of the retinal architecture. Finally, elovl2 crispants showed differences in the visual motor reflex light off (VMR-OFF) at day 7 compared to controls. In sum, inactivation of elovl2 in zebrafish embryos caused changes in lipid composition and in visual behavior, further confirming the important role of LC-PUFAs in healthy vision.

ELOVL2‐methylation and renal and cardiovascular event in patients with chronic kidney disease

“…Experimental studies in mice and zebrafish have shown that inactivation of Elvol2 (i.e. knockout or down regulation) caused accelerated aging phenotype 7,26 . However, only partial improvement was seen after dietary supplementation of PUFAs in Elovl2‐ knockout mice, 8 suggesting that Elvol2 may affect pathways other than PUFAs.…”

A set of common buccal CpGs that predict epigenetic age and associate with lifespan-regulating genes

“…Creating a point mutation in Elovl2 disrupts the enzymatic activity of Elovl2, causes premature visual decline, and leads to the early accumulation of age-related autofluorescent deposits in mice ( Chen et al., 2020 ). In zebrafish, inactivating elovl2 alters lipid composition, increases retinal thickness, and perturbs visual behavior ( Dasyani et al., 2020 ). The deletion of Elovl2 reduces lifespan and induces an accelerated aging phenotype in mice characterized by early hair loss as well as impairments in bone density, endurance, muscle strength, learning, and memory ( Li et al., 2022 ).…”

Dynamic Progress in Technological Advances to Study Lipids in Aging: Challenges and Future Directions

“…Nano-injection of lipids has been successful in directly delivering different phospholipids, including PE, PC, and LPC, into intracellular membranes ( Aref et al, 2020 ). Powerful genetic tools, such as CRISPR-Cas9 mediated knockouts, have created programmable, robust and versatile methods for genome editing across several organisms ( Chen et al, 2020b ; Dasyani et al, 2020 ). However, classical approaches offer only binary or on/off control of gene expression.…”