Open Readings 2025 • P3-82
MATERNAL HIGH-FAT DIET EFFECT ON THE OFFSPRINGS RETINAL INFLAMMATORY RESPONSE
Patricija Čepauskytė1, Gintarė Urbonaitė1, Neda Ieva Biliūtė1, 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: Increased high-fat content in today’s society’s diet is one of the leading factors contributing to the rising obesity rates. Research studies show that maternal high-fat diet (mHFD) can be the cause of neurodevelopmental disorders in the offspring due to induced systemic inflammation [1, 2, 3]. Moreover, inflammatory response changes throughout different pahses of female mice estrous cycle [4, 5, 6]. Proteins such as CD68 and TSPO can be used as dependable biomarkers for detecting microglia phagocytic and metabolic activation, and identifying inflammatory response in the central nervous system, which also includes the retina [7,8]. Although some studies show HFD effect on the retina, little research has been done to investigate its impact on the offspring retina [9]. This study aims to evaluate maternal diet induced changes of microglial CD68 and TSPO area and Müller cell activity in the peripheral retina of the offspring and assess how they depend on the mice female estrous cycle phases.
Methods: Female C57Bl/6J mice, from weaning and during pairing, pregnancy and lactation, were fed with either control diet (CD, 10% fat) or high-fat diet (HFD, 60% fat). The offspring were weaned to normal rodient diet. Collected eyeballs of the offspring were fixed with 4% PFA, cryoprotected, and sliced using cryotome. Microglia, Müller cells, CD68 and TSPO proteins in microglia were labeled immunohistochemically using anti-RFP, anti-GFAP, anti-CD68, and anti-TSPO antibodies, respectively. Before tissue collection, the estrous cycle phases were determined by vaginal cytology of 22-week-old female offspring.
Results: We evaluated mHFD effect on offspring Müller cells, microglia cells, CD68 and TSPO area in microglia cells in peripheral retina. Our results revealed that mHFD significantly increased the area of microglia, Müller cells, CD68 and TSPO in both male and female offspring’s peripheral retina. However, we observed a more subtle mHFD effect on female offspring retina. Further research confirmed that these different mHFD alterations could be due to female hormone changes during female estrous cycle.
Conclusion: Our findings demonstrated that mHFD had an effect on both male and female offspring peripheral retina, and that the inflammatory response of the retina could be dependent on reproductive hormones.
Funding: This work was supported by the Science Promotion Fund of Vilnius University.
[1] 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.
[2] R. D. Oades, A.-M. Myint, M. R. Dauvermann, B. G. Schimmelmann, and M. J. Schwarz, ‘Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention’, p. 19, 2010.
[3] 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.
[4] Villa A, Vegeto E, Poletti A, Maggi A. Estrogens, Neuroinflammation, and Neurodegeneration. Endocr Rev. 2016 Aug;37(4):372-402. doi: 10.1210/er.2016-1007. Epub 2016 May 19. PMID: 27196727; PMCID: PMC4971309.
[5] Crespo-Castrillo, A., & Arevalo, M. A. (2020). Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation. International journal of molecular sciences, 21(9), 3219. https://doi.org/10.3390/ijms21093219.
[6] Benlloch-Navarro, S., Trachsel-Moncho, L., Fernández-Carbonell, Á., Olivar, T., Soria, J. M., Almansa, I., & Miranda, M. (2019). Progesterone anti-inflammatory properties in hereditary retinal degeneration. The Journal of steroid biochemistry and molecular biology, 189, 291–301. https://doi.org/10.1016/j.jsbmb.2019.01.007.
[7] Fu R, Shen Q, Xu P, Luo JJ, Tang Y. Phagocytosis of microglia in the central nervous system diseases. Mol Neurobiol. 2014 Jun;49(3):1422-34. doi: 10.1007/s12035-013-8620-6. Epub 2014 Jan 7. PMID: 24395130; PMCID: PMC4012154.
[8] Hector, M., Langmann, T., & Wolf, A. (2024). Translocator protein (18 kDa) (Tspo) in the retina and implications for ocular diseases. Progress in retinal and eye research, 100, 101249. https://doi.org/10.1016/j.preteyeres.2024.101249.
[9] 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.
