Association between Disorders of Lipid Metabolism and Oculopathy: An Overview

Figures

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  Figure 1. Relationship between disorders of lipid metabolism and oculopathy. Created in BioRender. 1, 1. (2025) https://BioRender.com/avh63pc.

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  Figure 2. Relationship between disorders of lipid metabolism and the progression of keratoconus. Lipid accumulation in the body affects corneal health in a number of ways. Lipid deposition leads to the aggregation of lipid droplets within corneal endothelial cells (CECs), which results in decreased density of CECs, distorted cell morphology, disruption of intercellular tight junctions and adhesion junctions, reduction in the number of surface microvilli, reduction in the expression and function of intracellular Na+/K+-ATPase, imbalance in the concentration of sodium and potassium ions, activation of oxidative stress and mitochondrial dysfunction, and ultimately, corneal endothelial cytotoxicity and apoptosis. Meanwhile, lipids are initially distributed as low-density lipoproteins (LDL) around blood vessels and leak into tissues through an insulating process, after which LDL interacts with 2-acrylamide-2-methylpropanesulfonic acid (AMPS) to form LDL-AMPS complexes, which are selectively entrapped to different parts of the eye, and then phagocytosis uptakes and degrades the LDL-AMPS complexes and then releases the Cholesterol and other lipids are released into the ocular tissues, causing…

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  Figure 3. Association between disorders of lipid metabolism and cataracts. Disorders of lipid metabolism and imbalances in lipid peroxide (LPO) levels reduce the activity of the Na+/K+-ATPase enzyme, leading to sodium ion accumulation in the lens, osmotic pressure and electrolyte imbalances, and water influx into the lens, resulting in lens edema and cortical liquefaction. Also, metabolic disorders cause oxidation of polyunsaturated fatty acids PUFAs in cell membranes to produce malondialdehyde (MDA), resulting in protein damage. In addition, lipid imbalance also triggers oxidative stress. On the one hand, the generated reactive oxygen species attack protein sulfhydryl groups (-SH), denaturing proteins and forming disulfide bonds (-S-S-), which leads to protein aggregation; on the other hand, oxidative stress decreases the function of lens epithelial cells and reduces the function of α-lens proteins, which can likewise lead to denaturation and aggregation of proteins. The combined effect of these mechanisms contributes to the development of cataract. Created in BioRender. 1, 1. (2025) https://BioRender.com/rtb0ufa.

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  Figure 4. Link between disorders of lipid metabolism and the pathogenesis of glaucoma. Lipid metabolism disorders, with increased saturated fatty acids in the body, trigger endoplasmic reticulum stress (ERS), exacerbate mitochondrial dysfunction and reactive oxygen species production, activate the JNK/p38 MAPK pathway, and an imbalance in the Bax/Bcl-2 ratio, causing apoptosis of the retinal ganglion cells (RGC). Lipids also promote atherosclerosis and vascular endothelial cell damage, resulting in microcirculatory impairment of blood flow, reduced blood supply, and decreased blood supply to the optic nerve from the short posterior ciliary artery, leading to optic nerve atrophy. In addition, lipid disorders affect SREPB-1 expression, resulting in lipid deposition in the trabecular meshwork, causing lectin-like oxidized LDL receptor-1 (Lox-1) uptake of oxidized LDL, activation of the NF-kB signaling pathway, and elevated expression of IL-6 and TNF-α, resulting in inflammatory damage to the optic nerve. Lipid deposition in the trabecular meshwork also causes oxidative stress and remodeling of the trabecular meshwork extracellular matrix (ECM), resulting in trabecular meshwork cellular…

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  Figure 5. Mechanism of action between disorders of lipid metabolism and the development of diabetic retinal degeneration. Disorders of lipid metabolism cause aggregation of the monocyte macrophage system (MPS), which activates PPARγ signaling and affects Perilipin2 protein expression, resulting in capillary degeneration. Lipid deposition also causes changes in the expression of intercellular tight junction proteins (JAM, Occludin, and Claudin), which increases the permeability of the blood-retinal barrier and the infiltration of plasma components into the retina, causing changes in retinal structure. Abnormal lipid metabolism also affects the expression of various factors (LOX-1, HIF-1α, VEGF-A, NOX-1, NOX-2), activating oxidative stress and causing endothelial dysfunction (ETDF). In addition, lipid abnormalities lead to endoplasmic reticulum stress and mitochondrial dysfunction, reactive oxygen species (ROS) generation, and activation of STING signaling through the IRE1α-XBP1 axis in human retinal endothelial cells (HRVECs), triggering vascular endothelial (VE) inflammatory responses. Meanwhile, mitochondrial DNA from retinal endothelial cells leaks into the cytosol, and glycolipotoxicity…

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  Figure 6. Illustration of the association between disorders of lipid metabolism and age-related macular degeneration (AMD). Lipid metabolism disorders affect peroxidase expression levels, and the interaction between the two is such that peroxidase accumulates very long chain fatty acids (VLCFA), which are deposited on mitochondrial membranes affecting membrane fluidity, destabilizing the electron transport chain (ETC) complex, and leading to reduced ATP production and cell death. Peroxidase also blocks glucose oxidation by inhibiting pyruvate dehydrogenase (PDH) activity, leading to retinal photoreceptor cell (PRC), muller cell, and ganglion damage, macular edema, and an inflammatory response that results in an imbalance of apolipoproteins (APOEs) and complement, leading to the development of vitreous warts. In addition peroxidase induces oxidative stress and changes in the NAD(+)/NADH redox state, leading to the release of cytochrome C from the mitochondria, dysregulation of the expression of Sirtuins and HIF-1α, and ultimately retinal pigment epithelial (RPE) cell death. Together, these mechanisms contribute to the development of AMD. Created in BioRender. 1, 1. (2025)…