Dietary Omega-3 Fatty Acids Deficiency Affects the Glutamatergic Transport System in Rat Retina: Modulatory Effects after High Intraocular Pressure

Letícia V. Siqueira, Eduardo P. Rico, Mário C. Bulla, Luciano Bellini, Luiz C. L. Silveira, Lúcia Vinadé, Diogo O. Souza, Júlia D. Moreira

Biochemistry Department, Basic Sciences of Health Institute, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Department of Nutrition, Health Sciences Centre, Federal University of Santa Catarina, Campus Universitário Trindade, Florianópolis, Brazil.
Master Graduation Program in Biological Sciences, Campus S?o Gabriel, Federal University of Pampa—UNIPAMPA, S?o Gabriel, Brazil.
Phy- siology Department, Biological Science Center, Federal University of Pará, Belém, Brazil.

DOI: 10.4236/fns.2013.49A1027                

Abstract

Glutamate excitotoxicity has been postulated as a putative mechanism involved in the physiopathology of glaucoma, a disease that can cause retinal cell damage. Thus, the modulation of glutamatergic parameters is a putative therapeutic target to prevent excitotoxic retinal injury. Here, we investigated the effect of dietary omega-3 fatty acids (w3) in the retinal glutamate transport system in basal and ischemic conditions. Female Wistar rats were divided into two groups: w3 diet (w3 group) and w3 deficient-diet (D group). Their pups, at 60 days old, were used for the experiments. Retinal ischemia, a mechanism involved in the physiopathology of glaucoma, was induced by high intraocular pressure (HIOP, 140 180 mmHg for 45 min) to impair retinal blood flow. Analyses were performed 7 days after ischemia. The D group showed a decreased glutamate uptake in basal conditions and after HIOP when compared to the w3 group. After HIOP, there was a decrease in glutamate uptake in the D group that was not observed in the w3 group (p < 0.005). Concerning glutamate transporters, the w3 group presented higher levels of GLT-1 compared to the D group in basal and ischemic conditions. After HIOP, EAAC1 was increased in both groups, while GLT-1 increased only in the D group, compared to basal levels. GLAST and EAAT5 presented no alterations. The modulation of the glutamatergic system by dietary w3 fatty acids points to a potential mechanism by which w3 PUFAs exert beneficial effects in the retina.

Keywords

N-3 PUFAs; Retina; Ischemia; HIOP; Glaucoma; Glutamate Transporters

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	A. V. Tzingounis and J. I. Wadiche, “Glutamate Transporters: Confining Runaway Excitation by Shaping Synaptic Transmission,” Nature Reviews Neuroscience, Vol. 8, No. 12, 2007, pp. 935-947. doi:10.1038/nrn2274
[2]	A. Bringmann, T. Pannicke, B. Biedermann, M. Francke, I. Iandiev, J. Grosche, P. Wiedemann, J. Albrecht and A. Reichenbach, “Role of Retinal Glial Cells in Neurotransmitter Uptake and Metabolism,” Neurochemistry International, Vol. 54, No. 3-4, 2009, pp. 143-160. doi:10.1016/j.neuint.2008.10.014
[3]	J. Ambati, K. V. Chalam, D. K. Chawla, C. T. D’Angio, E. G. Guillet, S. J. Rose, R. E. Vanderlinde and B. K. Ambati, “Elevated Gamma-Aminobutyric Acid, Glutamate, and Vascular Endothelial Growth Factor Levels in the Vitreous of Patients With Proliferative Diabetic Retinopathy,” Archives of Ophthalmology, Vol. 115, No. 9, 1997, pp. 1161-1166. doi:10.1001/archopht.1997.01100160331011
[4]	D. E. Brooks, G. A. Garcia, E. B. Dreyer, D. Zurakowski and R. E. Franco-Bourland, “Vitreous Body Glutamate Concentration in Dogs with Glaucoma,” American Journal of Veterinary Research, Vol. 58, No. 8, 1997, pp. 864-867.
[5]	K. R. Martin, H. Levkovitch-Verbin, D. Valenta, L. Baumrind, M. E. Pease and H. A. Quigley, “Retinal Glutamate Transporter Changes in Experimental Glaucoma and after Optic Nerve Transection in the Rat,” Investigative Ophthalmology & Visual Science, Vol. 43, No. 7, 2002, pp. 2236-2243.
[6]	A. Bringmann, T. Pannicke, J. Grosche, M. Francke, P. Wiedemann, S. N. Skatchkov, N. N. Osborne and A. Reichenbach, “Muller Cells in the Healthy and Diseased Retina,” Progress in Retinal and Eye Research, Vol. 25, No. 4, 2006, pp. 397-424. doi:10.1016/j.preteyeres.2006.05.003
[7]	D. J. Holcombe, N. Lengefeld, G. A. Gole and N. L. Barnett, “The Effects of Acute Intraocular Pressure Elevation on Rat Retinal Glutamate Transport,” Acta Ophthalmologica, Vol. 86, No. 4, 2008, pp. 408-414. doi:10.1111/j.1600-0420.2007.01052.x
[8]	T. Rauen, W. R. Taylor, K. Kuhlbrodt and M. Wiessner, “High-Affinity Glutamate Transporters in the Rat Retina: A Major Role of the Glial Glutamate Transporter Glast-1 in Transmitter Clearance,” Cell and Tissue Research, Vol. 291, No. 1, 1998, pp. 19-31. doi:10.1007/s004410050976
[9]	D. V. Pow and N. L. Barnett, “Changing Patterns of Spatial Buffering of Glutamate in Developing Rat Retinae Are Mediated by the Muller Cell Glutamate Transporter GLAST,” Cell and Tissue Research, Vol. 297, No. 1, 1999, pp. 57-66. doi:10.1007/s004410051333
[10]	T. Rauen and B. I. Kanner, “Localization of the Glutamate Transporter GLT-1 in Rat and Macaque Monkey Retinae,” Neuroscience Letters, Vol. 169, No. 1-2, 1994, pp. 137-140. doi:10.1016/0304-3940(94)90375-1
[11]	T. Rauen, J. D. Rothstein and H. Wassle, “Differential Expression of Three Glutamate Transporter Subtypes in the Rat Retina,” Cell and Tissue Research, Vol. 286, No. 3, 1996, pp. 325-336. doi:10.1007/s004410050702
[12]	M. Wiessner, E. L. Fletcher, F. Fischer and T. Rauen, “Localization and Possible Function of the Glutamate Transporter, EAAC1, in the Rat Retina,” Cell and Tissue Research, Vol. 310, No. 1, 2002, pp. 31-40. doi:10.1007/s00441-002-0612-1
[13]	D. V. Pow and N. L. Barnett, “Developmental Expression of Excitatory Amino Acid Transporter 5: A Photoreceptor and Bipolar Cell Glutamate Transporter in Rat Retina,” Neuroscience Letters, Vol. 280, No. 1, 2000, pp. 21-24. doi:10.1016/S0304-3940(99)00988-X
[14]	N. L. Barnett and S. D. Grozdanic, “Glutamate Transporter Localization Does Not Correspond to the Temporary Functional Recovery and Late Degeneration after Acute Ocular Ischemia in Rats,” Experimental Eye Research, Vol. 79, No. 4, 2004, pp. 513-524. doi:10.1016/j.exer.2004.06.022
[15]	M. M. Ward, A. I. Jobling, T. Puthussery, L. E. Foster and E. L. Fletcher, “Localization and Expression of the Glutamate Transporter, Excitatory Amino Acid Transporter 4, within Astrocytes of the Rat Retina,” Cell and Tissue Research, Vol. 315, No. 3, 2004, pp. 305-310. doi:10.1007/s00441-003-0849-3
[16]	B. Fyk-Kolodziej, P. Qin, A. Dzhagaryan and R. G. Pourcho, “Differential Cellular and Subcellular Distribution of Glutamate Transporters in the Cat Retina,” Visual Neuroscience, Vol. 21, No. 4, 2004, pp. 551-565. doi:10.1017/S0952523804214067
[17]	A. Lee, A. R. Anderson, N. L. Barnett, M. G. Stevens and D. V. Pow, “Alternate Splicing and Expression of the Glutamate Transporter EAAT5 in the Rat Retina,” Gene, Vol. 506, No. 2, 2012, pp. 283-288. doi:10.1016/j.gene.2012.07.010
[18]	A. Lee, A. R. Anderson, S. J. Beasley, N. L. Barnett, P. Poronnik and D. V. Pow, “A New Splice Variant of the Glutamate-Aspartate Transporter: Cloning and Immunolocalization of GLAST1c in Rat, Pig and Human Brains,” Journal of Chemical Neuroanatomy, Vol. 43, No. 1, 2012, pp. 52-63. doi:10.1016/j.jchemneu.2011.10.005
[19]	G. A. Napper and M. Kalloniatis, “Neurochemical Changes Following Postmortem Ischemia in the Rat Retina,” Visual Neuroscience, Vol. 16, No. 6, 1999, pp. 11691180. doi:10.1017/S0952523899166161
[20]	N. L. Barnett, D. V. Pow, N. D. Bull, “Differential Perturbation of Neuronal and Glial Glutamate Transport Systems in Retinal Ischaemia,” Neurochemistry International, Vol. 39, No. 4, 2001, pp. 291-299. doi:10.1016/S0197-0186(01)00033-X
[21]	Q. Li and D. G. Puro, “Diabetes-Induced Dysfunction of the Glutamate Transporter in Retinal Muller Cells,” Investigative Ophthalmology & Visual Science, Vol. 43, No. 9, 2002, pp. 3109-3116.
[22]	T. T. Lam, J. M. Kwong and M. O. Tso, “Early Glial Responses after Acute Elevated Intraocular Pressure in Rats,” Investigative Ophthalmology & Visual Science, Vol. 44, No. 2, 2003, pp. 638-645. doi:10.1167/iovs.02-0255
[23]	N. N. Osborne, R. J. Casson, J. P. Wood, G. Chidlow, M. Graham and J. Melena, “Retinal Ischemia: Mechanisms of Damage and Potential Therapeutic Strategies,” Progress in Retinal and Eye Research, Vol. 23, No. 1, 2004, pp. 91-147. doi:10.1016/j.preteyeres.2003.12.001
[24]	M. Neuringer and W. E. Connor, “n-3 Fatty Acids in the Brain and Retina: Evidence for Their Essentiality,” Nutrition Reviews, Vol. 44, No. 9, 1986, pp. 285-294. doi:10.1111/j.1753-4887.1986.tb07660.x
[25]	N. G. Bazan, “Cell Survival Matters: Docosahexaenoic Acid Signaling, Neuroprotection and Photoreceptors,” Trends in Neurosciences, Vol. 29, No. 5, 2006, pp. 263271. doi:10.1016/j.tins.2006.03.005
[26]	N. G. Bazan, “Neuroprotectin D1-Mediated Anti-Inflammatory and Survival Signaling in Stroke, Retinal Degenerations, and Alzheimer’s Disease,” The Journal of Lipid Research, Vol. 50, 2009, pp. S400-S405. doi:10.1194/jlr.R800068-JLR200
[27]	M. Neuringer, W. E. Connor, D. S. Lin, L. Barstad and S. Luck, “Biochemical and Functional Effects of Prenatal and Postnatal Omega 3 Fatty Acid Deficiency on Retina and Brain in Rhesus Monkeys,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 83, No. 11, 1986, pp. 4021-4025. doi:10.1073/pnas.83.11.4021
[28]	H. S. Weisinger, A. J. Vingrys, L. Abedin and A. J. Sinclair, “Effect of Diet on the Rate of Depletion of n-3 Fatty Acids in the Retina of the Guinea Pig,” Journal of Lipid Research, Vol. 39, No. 6, 1998, pp. 1274-1279.
[29]	G. J. Anderson, M. Neuringer, D. S. Lin and W. E. Connor, “Can Prenatal N-3 Fatty Acid Deficiency Be Completely Reversed after Birth? Effects on Retinal and Brain Biochemistry and Visual Function in Rhesus Monkeys,” Pediatric Research, Vol. 58, No. 5, 2005, pp. 865-872. doi:10.1203/01.pdr.0000182188.31596.5a
[30]	C. L. Jensen, R. G. Voigt, T. C. Prager, Y. L. Zou, J. K. Fraley, J. C. Rozelle, M. R. Turcich, A. M. Llorente, R. E. Anderson and W. C. Heird, “Effects of Maternal Docosahexaenoic Acid Intake on Visual Function and Neurodevelopment in Breastfed Term Infants,” The American Journal of Clinical Nutrition, Vol. 82, No. 1, 2005, pp. 125-132.
[31]	K. Moriguchi, T. Yuri, K. Yoshizawa, K. Kiuchi, H. Takada, Y. Inoue, T. Hada, M. Matsumura and A. Tsubura, “Dietary Docosahexaenoic Acid Protects against N-Methyl-N-nitrosourea-Induced Retinal Degeneration in Rats,” Experimental Eye Research, Vol. 77, No. 2, 2003, pp. 167-173. doi:10.1016/S0014-4835(03)00114-3
[32]	A. Garelli, N. P. Rotstein and L. E. Politi, “Docosahexaenoic Acid Promotes Photoreceptor Differentiation without Altering Crx Expression,” Investigative Ophthalmology & Visual Science, Vol. 47, No. 7, 2006, pp. 30173027. doi:10.1167/iovs.05-1659
[33]	O. Miyauchi, A. Mizota, E. Adachi-Usami and M. Nishikawa, “Protective Effect of Docosahexaenoic Acid against Retinal Ischemic Injury: An Electroretinographic Study,” Ophthalmic Research, Vol. 33, No. 4, 2001, pp. 191-195. doi:10.1159/000055669
[34]	K. Murayama, S. Yoneya, O. Miyauchi, E. Adachi-Usami and M. Nishikawa, “Fish Oil (Polyunsaturated Fatty Acid) Prevents Ischemic-Induced Injury in the Mammalian Retina,” Experimental Eye Research, Vol. 74, No. 6, 2002, pp. 671-676. doi:10.1006/exer.2002.1151
[35]	J. D. Moreira, L. Knorr, M. Ganzella, A. P. Thomazi, C. G. de Souza, D. G. de Souza, C. F. Pitta, T. Mello e Souza, S. Wofchuk, E. Elisabetsky, L. Vinade, M. L. Perry and D. O. Souza, “Omega-3 Fatty Acids Deprivation Affects Ontogeny of Glutamatergic Synapses in Rats: Relevance for Behavior Alterations,” Neurochemistry International, Vol. 56, No. 6-7, 2010, pp. 753-759. doi:10.1016/j.neuint.2010.02.010
[36]	J. C. Dreixler, A. R. Shaikh, M. Alexander, B. Savoie and S. Roth, “Post-Ischemic Conditioning in the Rat Retina Is Dependent Upon Ischemia Duration and Is Not Additive with Ischemic Pre-Conditioning,” Experimental Eye Research, Vol. 91, No. 6, 2010, pp. 844-852. doi:10.1016/j.exer.2010.06.015
[37]	T. Pannicke, I. Iandiev, O. Uckermann, B. Biedermann, F. Kutzera, P. Wiedemann, H. Wolburg, A. Reichenbach and A. Bringmann “A Potassium Channel-Linked Mechanism of Glial Cell Swelling in the Postischemic Retina,” Molecular and Cellular Neuroscience, Vol. 26, No. 4, 2004, pp. 493-502. doi:10.1016/j.mcn.2004.04.005
[38]	C. K. Park, J. Cha, S. C. Park, P. Y. Lee, J. H. Kim, H. S. Kim, S. A. Kim, I. B. Kim and M. H. Chun, “Differential Expression of Two Glutamate Transporters, GLAST and GLT-1, in an Experimental Rat Model of Glaucoma,” Experimental Brain Research, Vol. 197, No. 2, 2009, pp. 101-109. doi:10.1007/s00221-009-1896-0
[39]	T. Harada, C. Harada, K. Nakamura, H. M. Quah, A. Okumura, K. Namekata, T. Saeki, M.Aihara, H. Yoshida, A. Mitani and K. Tanaka, “The Potential Role of Glutamate Transporters in the Pathogenesis of Normal Tension Glaucoma,” Journal of Clinical Investigation, Vol. 117, No. 7, 2007, pp. 1763-1770. doi:10.1172/JCI30178
[40]	K. Namekata, C. Harada, X. Guo, K. Kikushima, A. Kimura, N. Fuse, Y. Mitamura, K. Kohyama, Y. Matsumoto, K. Tanaka and T. Harada, “Interleukin-1 Attenuates Normal Tension Glaucoma-Like Retinal Degeneration in EAAC1-Deficient Mice,” Neuroscience Letters, Vol. 465, No. 2, 2009, pp. 160-164. doi:10.1016/j.neulet.2009.09.029
[41]	J. L. Arriza, S. Eliasof, M. P. Kavanaugh, S. G. Amara, “Excitatory Amino Acid Transporter 5, a Retinal Glutamate Transporter Coupled to a Chloride Conductance,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 8, 1997, pp. 41554160.
[42]	E. Wersinger, Y. Schwab, J. A. Sahel, A. Rendon, D. V. Pow, S. Picaud and M. J. Roux, “The Glutamate Transporter EAAT5 Works as a Presynaptic Receptor in Mouse Rod Bipolar Cells,” The Journal of Physiology, Vol. 577, No. , 2006, pp. 221-234.
[43]	R. D. O’Brien, 2004 “Fats and Oils: Formulating and Processing for Application,” 2nd Edition, CRC Press, USA.