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Potential role of polyunsaturated fatty acids in diabetic retinopathy.

Shen J, Bi YL, Das UN - Arch Med Sci (2014)

Bottom Line: Recent studies suggest that polyunsaturated fatty acids (PUFAs) and their metabolites could play a significant role in DR.There is evidence to suggest that an imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DR.This implies that PUFAs and their metabolites that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DR.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

ABSTRACT
Diabetic retinopathy (DR) is a serious complication of long-standing diabetes mellitus. It affects about 25% of all patients with diabetes mellitus and causes a significant decrease in the quality of life. Despite many years of research, the exact pathway that leads to the development and progression of DR is not clear. Recent studies suggest that polyunsaturated fatty acids (PUFAs) and their metabolites could play a significant role in DR. There is evidence to suggest that an imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DR. This implies that PUFAs and their metabolites that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DR.

No MeSH data available.


Related in: MedlinePlus

Metabolism of AA after its release from cell membrane lipid pool by the activation of phospholipase A2 on exposure to hormones, growth factors and cytokines. The PGHSs metabolize AA to prostaglandins, thromboxanes and prostacyclin. LOXs metabolize AA to leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins. The P450 monooxygenases metabolize AA to mid-chain HETEs, ω-3 terminal HETEs and the epoxyeicosatrienoic acids (EETs). The EETs have anti-inflammatory actions and so are likely to play a role in DR. Even EPA undergoes the same metabolic fate as is shown for AA here
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Figure 0002: Metabolism of AA after its release from cell membrane lipid pool by the activation of phospholipase A2 on exposure to hormones, growth factors and cytokines. The PGHSs metabolize AA to prostaglandins, thromboxanes and prostacyclin. LOXs metabolize AA to leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins. The P450 monooxygenases metabolize AA to mid-chain HETEs, ω-3 terminal HETEs and the epoxyeicosatrienoic acids (EETs). The EETs have anti-inflammatory actions and so are likely to play a role in DR. Even EPA undergoes the same metabolic fate as is shown for AA here

Mentions: Essential fatty acids (EFAs) n-3 α-linolenic acid (ALA) and n-6 linoleic acid (LA) are widely distributed in our diet. It is believed that both n-3 and n-6 EFAs are metabolized by the same set of enzymes Δ6 and Δ5 desaturases and elongases into their long-chain metabolites, ALA to eicosapentaenoic and docosahexaenoic acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) respectively) and LA to arachidonic acid (AA) (Figure 1) [13–15]. Both EFAs and their long-chain metabolites AA, EPA and DHA are incorporated mainly into the phospholipid (PL) fraction of the cell membrane. In response to various stimuli including growth factors, cytokines and free radicals, phospholipase A2 (PLA2) is activated leading to the release of AA, EPA and DHA, which are converted to their respective eicosanoids. The AA, EPA and DHA are metabolized by cyclo-oxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP450) enzymes, which results in the formation of several products (Figure 2). The AA forms a precursor to pro-inflammatory prostaglandins and thromboxanes of 2 series and leukotrienes of 4 series (though not all prostaglandins formed are pro-inflammatory. For instance prostacyclin from AA and prostaglandin E1 (PGE1) from DGLA have anti-inflammatory actions), whereas EPA forms precursor to 3 series prostaglandins, thromboxanes and 5 series leukotrienes. It is noteworthy that AA can also give rise to lipoxins, which are potent anti-inflammatory molecules. Similarly, EPA gives rise to resolvins and DHA to protectins, which possess significant anti-inflammatory and wound healing properties and show cytoprotective actions. Thus, AA, EPA and DHA, under defined conditions, form specific anti-inflammatory lipoxins, resolvins and protectins respectively that protect various cells and tissues against insults and augment recovery of the target tissues and organs to normal and reestablish homeostasis. Since the retina and brain are rich in AA, DHA and EPA (DHA > AA > EPA), it is reasonable to assume that adequate amounts of lipoxins, resolvins and protectins are formed under normal physiological conditions to protect the retina and other neuronal cells from various insults and diseases [13–15]. This evidence indicates that PUFAs are not only biologically active by themselves but are also capable of giving rise to several biologically active metabolites that play an important role in physiological and pathological processes.


Potential role of polyunsaturated fatty acids in diabetic retinopathy.

Shen J, Bi YL, Das UN - Arch Med Sci (2014)

Metabolism of AA after its release from cell membrane lipid pool by the activation of phospholipase A2 on exposure to hormones, growth factors and cytokines. The PGHSs metabolize AA to prostaglandins, thromboxanes and prostacyclin. LOXs metabolize AA to leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins. The P450 monooxygenases metabolize AA to mid-chain HETEs, ω-3 terminal HETEs and the epoxyeicosatrienoic acids (EETs). The EETs have anti-inflammatory actions and so are likely to play a role in DR. Even EPA undergoes the same metabolic fate as is shown for AA here
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296072&req=5

Figure 0002: Metabolism of AA after its release from cell membrane lipid pool by the activation of phospholipase A2 on exposure to hormones, growth factors and cytokines. The PGHSs metabolize AA to prostaglandins, thromboxanes and prostacyclin. LOXs metabolize AA to leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins. The P450 monooxygenases metabolize AA to mid-chain HETEs, ω-3 terminal HETEs and the epoxyeicosatrienoic acids (EETs). The EETs have anti-inflammatory actions and so are likely to play a role in DR. Even EPA undergoes the same metabolic fate as is shown for AA here
Mentions: Essential fatty acids (EFAs) n-3 α-linolenic acid (ALA) and n-6 linoleic acid (LA) are widely distributed in our diet. It is believed that both n-3 and n-6 EFAs are metabolized by the same set of enzymes Δ6 and Δ5 desaturases and elongases into their long-chain metabolites, ALA to eicosapentaenoic and docosahexaenoic acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) respectively) and LA to arachidonic acid (AA) (Figure 1) [13–15]. Both EFAs and their long-chain metabolites AA, EPA and DHA are incorporated mainly into the phospholipid (PL) fraction of the cell membrane. In response to various stimuli including growth factors, cytokines and free radicals, phospholipase A2 (PLA2) is activated leading to the release of AA, EPA and DHA, which are converted to their respective eicosanoids. The AA, EPA and DHA are metabolized by cyclo-oxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP450) enzymes, which results in the formation of several products (Figure 2). The AA forms a precursor to pro-inflammatory prostaglandins and thromboxanes of 2 series and leukotrienes of 4 series (though not all prostaglandins formed are pro-inflammatory. For instance prostacyclin from AA and prostaglandin E1 (PGE1) from DGLA have anti-inflammatory actions), whereas EPA forms precursor to 3 series prostaglandins, thromboxanes and 5 series leukotrienes. It is noteworthy that AA can also give rise to lipoxins, which are potent anti-inflammatory molecules. Similarly, EPA gives rise to resolvins and DHA to protectins, which possess significant anti-inflammatory and wound healing properties and show cytoprotective actions. Thus, AA, EPA and DHA, under defined conditions, form specific anti-inflammatory lipoxins, resolvins and protectins respectively that protect various cells and tissues against insults and augment recovery of the target tissues and organs to normal and reestablish homeostasis. Since the retina and brain are rich in AA, DHA and EPA (DHA > AA > EPA), it is reasonable to assume that adequate amounts of lipoxins, resolvins and protectins are formed under normal physiological conditions to protect the retina and other neuronal cells from various insults and diseases [13–15]. This evidence indicates that PUFAs are not only biologically active by themselves but are also capable of giving rise to several biologically active metabolites that play an important role in physiological and pathological processes.

Bottom Line: Recent studies suggest that polyunsaturated fatty acids (PUFAs) and their metabolites could play a significant role in DR.There is evidence to suggest that an imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DR.This implies that PUFAs and their metabolites that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DR.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

ABSTRACT
Diabetic retinopathy (DR) is a serious complication of long-standing diabetes mellitus. It affects about 25% of all patients with diabetes mellitus and causes a significant decrease in the quality of life. Despite many years of research, the exact pathway that leads to the development and progression of DR is not clear. Recent studies suggest that polyunsaturated fatty acids (PUFAs) and their metabolites could play a significant role in DR. There is evidence to suggest that an imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DR. This implies that PUFAs and their metabolites that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DR.

No MeSH data available.


Related in: MedlinePlus