THE EFFECT OF MATERNAL HIGH-FAT DIET ON OFFSPRING RETINA

Neda Ieva Biliūtė1, Gintarė Urbonaitė1, Guoda Laurinavičiūtė2, Urtė Neniškytė1, 3

1 Institute of Biosciences, Life Sciences Center, Vilnius University, Lithuania

2 Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Lithuania

3 VU-EMBL Partnership Institute, Life Sciences Center, Vilnius University, Lithuania

[email protected]

Aim: Today Western diet has increasing content of fats, and this leads to increasing obesity rates. Many studies show that maternal high-fat diet causes chronic inflammation which can lead to neurodevelopmental disorders of the offspring [1, 2, 3]. It has been shown that the retina, as a part of central nervous system, is also affected in the individuals consuming high-fat diet [4, 5, 6]. However, there are no studies investigating the effect of maternal high-fat diet on the retina of the offspring. In this study we aim to determine whether maternal high-fat diet leads to retinal changes in the offspring.

Methods: We fed female C57Bl/6J mice with a control diet (10% fat) or high-fat diet (60% fat) from weaning to lactation. The offspring were weaned to CD. The eyeballs of the offspring were collected, fixed with 4% PFA, cryoprotected and sliced using cryotome. Retinal ganglion cells, Müller cells and microglia cells were labeled immunohistochemically using anti-RBPMS, anti-GFAP and Iba1 antibodies, respectively.

Results: We evaluated the thickness of retinal layers, density of retinal ganglion cells and microglia cells, GFAP and Iba1 signal area. The measurements were compared between the groups of offspring. No significant changes were found in the layer thicknesses of the peripheral retina. Outer nuclear layer of the central retina was significantly thicker in male offspring of maternal high-fat diet group compared to the male offspring of maternal control diet group. Density of the retinal ganglion cell did not differ significantly between the groups. There were no significant differences in the GFAP signal area and Iba1 signal area between the groups. Microglia density was significantly higher in maternal high-fat diet female offspring compared to maternal control diet female offspring in peripheral and central retina. However, in the male offspring the microglia density was lower in the maternal high-fat diet group in the peripheral retina. Iba1 signal area was significantly larger in the peripheral retina of maternal high-fat diet female offspring and significantly lower in peripheral retina of maternal high-fat diet male offspring compared to maternal control diet offspring. No significant differences in Iba1 signal area were found on central retina of female and male offspring.

Conclusions: Our findings showed that maternal high-fat diet had a gender-specific effect on the morphology of offspring retina and activation of microglia in the retina.

Acknowledgments: This work was supported by the Science Promotion Fund of Vilnius University.


[1] S. S. Kang, A. Kurti, D. A. Fair, and J. D. Fryer, 'Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring', p. 12, 2014.

[2] R. D. Oades, A.-M. Myint, M. R. Dauvermann, B. G. Schimmelmann, and M. J. Schwarz, 'RAestetaerchntion-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention', p. 19, 2010.

[3] M. Maes, R. Verkerk, S. Bonaccorso, W. Ombelet, E. Bosmans, and S. Scharpé, 'Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation', Life Sciences, vol. 71, no. 16, pp. 1837-1848, Sep. 2002, doi: 10.1016/S0024-3205(02)01853-2.

[4] D. A. Clarkson-Townsend, A. J. Douglass, A. Singh, R. S. Allen, I. N. Uwaifo, and M. T. Pardue, 'Impacts of high fat diet on ocular outcomes in rodent models of visual disease', Experimental Eye Research, vol. 204, p. 108440, Mar. 2021, doi: 10.1016/j.exer.2021.108440.

[5] R. C.-A. Chang et al., 'High-Fat Diet–Induced Retinal Dysfunction', Invest. Ophthalmol. Vis. Sci., vol. 56, no. 4, p. 2367, Apr. 2015, doi: 10.1167/iovs.14-16143.

[6] J.-J. Lee et al., 'High-Fat Diet Induces Toll-Like Receptor 4-Dependent Macrophage/Microglial Cell Activation and Retinal Impairment', Invest. Ophthalmol. Vis. Sci., vol. 56, no. 5, p. 3041, May 2015, doi: 10.1167/iovs.15-16504.