TY  - JOUR
AU  - Jovanović Macura, Irena
AU  - Živanović, Ana
AU  - Perović, Milka
AU  - Ćirić, Jelena
AU  - Major, Tamara
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5121
AB  - Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease
VL  - 24
IS  - 18
DO  - 10.3390/ijms241814092
ER  - 

@article{
author = "Jovanović Macura, Irena and Živanović, Ana and Perović, Milka and Ćirić, Jelena and Major, Tamara and Kanazir, Selma and Ivković, Sanja",
year = "2023",
abstract = "Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease",
volume = "24",
number = "18",
doi = "10.3390/ijms241814092"
}

Jovanović Macura, I., Živanović, A., Perović, M., Ćirić, J., Major, T., Kanazir, S.,& Ivković, S.. (2023). The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease. in International Journal of Molecular Sciences
MDPI., 24(18).
https://doi.org/10.3390/ijms241814092

Jovanović Macura I, Živanović A, Perović M, Ćirić J, Major T, Kanazir S, Ivković S. The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease. in International Journal of Molecular Sciences. 2023;24(18).
doi:10.3390/ijms241814092 .

Jovanović Macura, Irena, Živanović, Ana, Perović, Milka, Ćirić, Jelena, Major, Tamara, Kanazir, Selma, Ivković, Sanja, "The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease" in International Journal of Molecular Sciences, 24, no. 18 (2023),
https://doi.org/10.3390/ijms241814092 . .

TY  - JOUR
AU  - Jovanović-Macura, Irena
AU  - Đuričić, Ivana
AU  - Major, Tamara
AU  - Milanović, Desanka
AU  - Šobajić, Slađana
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5543
AB  - Introduction: During fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression. Recently, higher doses of omega-3 supplementation have been recommended for pregnant women. Considering that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), play a crucial role in maintaining the delicate homeostasis required for the proper functioning of the retina and photoreceptors the effects of high-dose fish oil (FO) supplementation during pregnancy and lactation on the retina and retinal pigmented epithelium (RPE) in healthy offspring warrant better understanding. Methods: The fatty acid content and the changes in the expression of the genes regulating cholesterol homeostasis and DHA transport in the retina and RPE were evaluated following the high-dose FO supplementation. Results: Our study demonstrated that despite the high-dose FO treatment during pregnancy and lactation, the rigorous DHA homeostasis in the retina and RPE of the two-month-old offspring remained balanced. Another significant finding of this study is the increase in the expression levels of major facilitator superfamily domain-containing protein (Mfsd2a), a primary DHA transporter. Mfsd2a also serves as a major regulator of transcytosis during development, and a reduction in Mfsd2a levels poses a major risk for the development of leaky blood vessels. Conclusion: Impairment of the blood-retinal barrier (BRB) is associated with the development of numerous ocular diseases, and a better understanding of how to manipulate transcytosis in the BRB during development can enhance drug delivery through the BRB or contribute to the repair of central nervous system (CNS) barriers.
PB  - Frontiers Media SA
T2  - Frontiers in Nutrition
T1  - The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring
VL  - 10
SP  - 1330414
DO  - 10.3389/fnut.2023.1330414
ER  - 

@article{
author = "Jovanović-Macura, Irena and Đuričić, Ivana and Major, Tamara and Milanović, Desanka and Šobajić, Slađana and Kanazir, Selma and Ivković, Sanja",
year = "2023",
abstract = "Introduction: During fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression. Recently, higher doses of omega-3 supplementation have been recommended for pregnant women. Considering that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), play a crucial role in maintaining the delicate homeostasis required for the proper functioning of the retina and photoreceptors the effects of high-dose fish oil (FO) supplementation during pregnancy and lactation on the retina and retinal pigmented epithelium (RPE) in healthy offspring warrant better understanding. Methods: The fatty acid content and the changes in the expression of the genes regulating cholesterol homeostasis and DHA transport in the retina and RPE were evaluated following the high-dose FO supplementation. Results: Our study demonstrated that despite the high-dose FO treatment during pregnancy and lactation, the rigorous DHA homeostasis in the retina and RPE of the two-month-old offspring remained balanced. Another significant finding of this study is the increase in the expression levels of major facilitator superfamily domain-containing protein (Mfsd2a), a primary DHA transporter. Mfsd2a also serves as a major regulator of transcytosis during development, and a reduction in Mfsd2a levels poses a major risk for the development of leaky blood vessels. Conclusion: Impairment of the blood-retinal barrier (BRB) is associated with the development of numerous ocular diseases, and a better understanding of how to manipulate transcytosis in the BRB during development can enhance drug delivery through the BRB or contribute to the repair of central nervous system (CNS) barriers.",
publisher = "Frontiers Media SA",
journal = "Frontiers in Nutrition",
title = "The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring",
volume = "10",
pages = "1330414",
doi = "10.3389/fnut.2023.1330414"
}

Jovanović-Macura, I., Đuričić, I., Major, T., Milanović, D., Šobajić, S., Kanazir, S.,& Ivković, S.. (2023). The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring. in Frontiers in Nutrition
Frontiers Media SA., 10, 1330414.
https://doi.org/10.3389/fnut.2023.1330414

Jovanović-Macura I, Đuričić I, Major T, Milanović D, Šobajić S, Kanazir S, Ivković S. The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring. in Frontiers in Nutrition. 2023;10:1330414.
doi:10.3389/fnut.2023.1330414 .

Jovanović-Macura, Irena, Đuričić, Ivana, Major, Tamara, Milanović, Desanka, Šobajić, Slađana, Kanazir, Selma, Ivković, Sanja, "The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring" in Frontiers in Nutrition, 10 (2023):1330414,
https://doi.org/10.3389/fnut.2023.1330414 . .

TY  - JOUR
AU  - Jovanović Macura, Irena
AU  - Đuričić, Ivana
AU  - Major, Tamara
AU  - Milanović, Desanka
AU  - Brkić, Marjana
AU  - Šobajić, Slađana
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4309
AB  - The recommended fish oil (FO) supplementation doses often yield low omega-3 polyunsaturated fatty acids (PUFAs) tissue bioavailability, and higher doses (up to 10 g per day) have been increasingly recommended. However, the exact effects of such FO supplementation on the healthy retina and retinal pigmented epithelium (RPE) are unknown. Our study showed that the high dose FO treatment did not imbalance the rigorous docosahexaenoic acid (DHA, C22:6n3) homeostasis in the retina and RPE in the three-month-old female B6/SLJ mice. Instead, we have found the significant increase in the expression of Mfsd2a, the main DHA transporter. Mfsd2a is also an essential regulator of blood vessel transcytosis and the decrease in Mfsd2a expression can be a risk factor for developing leaky blood vessels. Therefore, the high-dose FO supplementation emerges as the prophylactic fortifier of the retinal blood vessels.
PB  - Elsevier Ltd
T2  - Journal of Functional Foods
T1  - The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice
VL  - 99
DO  - 10.1016/j.jff.2022.105302
ER  - 

@article{
author = "Jovanović Macura, Irena and Đuričić, Ivana and Major, Tamara and Milanović, Desanka and Brkić, Marjana and Šobajić, Slađana and Kanazir, Selma and Ivković, Sanja",
year = "2022",
abstract = "The recommended fish oil (FO) supplementation doses often yield low omega-3 polyunsaturated fatty acids (PUFAs) tissue bioavailability, and higher doses (up to 10 g per day) have been increasingly recommended. However, the exact effects of such FO supplementation on the healthy retina and retinal pigmented epithelium (RPE) are unknown. Our study showed that the high dose FO treatment did not imbalance the rigorous docosahexaenoic acid (DHA, C22:6n3) homeostasis in the retina and RPE in the three-month-old female B6/SLJ mice. Instead, we have found the significant increase in the expression of Mfsd2a, the main DHA transporter. Mfsd2a is also an essential regulator of blood vessel transcytosis and the decrease in Mfsd2a expression can be a risk factor for developing leaky blood vessels. Therefore, the high-dose FO supplementation emerges as the prophylactic fortifier of the retinal blood vessels.",
publisher = "Elsevier Ltd",
journal = "Journal of Functional Foods",
title = "The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice",
volume = "99",
doi = "10.1016/j.jff.2022.105302"
}

Jovanović Macura, I., Đuričić, I., Major, T., Milanović, D., Brkić, M., Šobajić, S., Kanazir, S.,& Ivković, S.. (2022). The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice. in Journal of Functional Foods
Elsevier Ltd., 99.
https://doi.org/10.1016/j.jff.2022.105302

Jovanović Macura I, Đuričić I, Major T, Milanović D, Brkić M, Šobajić S, Kanazir S, Ivković S. The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice. in Journal of Functional Foods. 2022;99.
doi:10.1016/j.jff.2022.105302 .

Jovanović Macura, Irena, Đuričić, Ivana, Major, Tamara, Milanović, Desanka, Brkić, Marjana, Šobajić, Slađana, Kanazir, Selma, Ivković, Sanja, "The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice" in Journal of Functional Foods, 99 (2022),
https://doi.org/10.1016/j.jff.2022.105302 . .