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Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress
Zhongjie Fu1, Chatarina A Lofqvist1, Zhuo Shao1
1From the Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA (ZF, ZS, YS, J-SJ, CGH, RZC, LPE, KT, JC, and LEHS); the Department of Ophthalmology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (CAL and AH); the Department of Pediatrics, Institute of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden (DL and IHP); and National Eye Institute, Division of Epidemiology and Clinical Research Clinical Trials Branch, National Eye Institute, NIH, Bethesda, MD (JPS).
Insights
Increasing adiponectin (APN) with omega-3 fatty acids may prevent retinopathy of prematurity (ROP). Supplementation in preterm infants
Area of Science:
- Ophthalmology
- Neonatology
- Nutritional Science
Background:
- Retinopathy of prematurity (ROP) is a leading cause of vision loss in premature infants.
- Serum adiponectin (APN) levels are linked to growth and gestational age, key ROP risk factors.
- Dietary omega-3 (ω-3) long-chain polyunsaturated fatty acids (LCPUFAs) show promise in suppressing ROP, but mechanisms are unclear.
Purpose of the Study:
- To investigate the role of adiponectin (APN) in the development of retinopathy of prematurity (ROP).
- To determine if dietary ω-3 LCPUFA supplementation elevates circulating APN concentrations to mediate protective effects against ROP.
Main Methods:
- Correlating serum APN and ω-3 LCPUFA levels with ROP in preterm infants.
- Utilizing a mouse model of oxygen-induced retinopathy (OIR) to assess the impact of ω-3 LCPUFA supplementation on serum APN and retinopathy.
Main Results:
- Low serum APN and ω-3 LCPUFA concentrations correlate with ROP in preterm infants.
- ω-3 LCPUFA feed increased total and bioactive high-molecular-weight APN in mice by reducing adipose endoplasmic reticulum stress.
- APN deficiency significantly reduced the protective effect of dietary ω-3 LCPUFA against neovascularization in mice.
Conclusions:
- Increasing APN levels through ω-3 LCPUFA supplementation may offer a strategy to suppress ROP in preterm infants.
- Adiponectin's role in the retina, particularly in neovessels, suggests a direct mechanism for its protective effects.
Background:
Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood.
Objective:
We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary ω-3 LCPUFAs to mediate the protective effect in ROP.
Design:
Serum APN concentrations were correlated with ROP development and serum ω-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether ω-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy.
Results:
We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum ω-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by ω-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. ω-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary ω-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels.
Conclusion:
Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.
