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Gholami S, Kamali Y, Reza Rostamzad M. Glycine Supplementation Ameliorates Retinal Neuronal Damage in an Experimental Model of Diabetes in Rats: A Light and Electron Microscopic Study. JOVR [Internet]. 2019Oct.24 [cited 2024Apr.24];14(4):448–456. Available from: https://knepublishing.com/index.php/JOVR/article/view/5449
https://doi.org/10.18502/jovr.v14i4.5449
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authors
-
Soghra Gholami
Soghra Gholami
Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
-
Younes Kamali
Younes Kamali
Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
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Mohammad Reza Rostamzad
Mohammad Reza Rostamzad
Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, International Division, Shiraz, Iran
Published Date
- Oct 24, 2019
Glycine Supplementation Ameliorates Retinal Neuronal Damage in an Experimental Model of Diabetes in Rats: A Light and Electron Microscopic Study
Abstract
Purpose: To investigate the potential neuroprotective effect of glycine supplementation on the retinal ultrastructure of streptozocin (STZ)-induced diabetic rats.
Methods: Adult male Wistar rats weighing 200–250 g (n = 40) were randomly divided into four groups of 10 each: normal group (C), glycine + normal group (G), STZ group (D), and glycine + STZ group (DG). The G and DG groups received glycine (130 mM and 1% w/v) freely in their drinking water seven days after the induction of diabetes for up to 16 weeks. Retinal samples for histopathology were examined using light and electron microscopy.
Results: Diabetes-induced histological changes were attenuated in the retinas of rats in the DG group. The ultrastructural alterations produced by experimental diabetes in the inner nuclear layer, outer nuclear layer, and ganglion cell layer were significantly ameliorated by glycine supplementation.
Conclusion: Our findings suggest that glycine supplementation effectively attenuates retinal neuronal damage in experimental diabetic rats, and thus may be a potential candidate to protect retinal ultrastructure against diabetes.
Keywords:
Diabetic Retinopathy, Electron Microscopy, Experimental, Glycine, Light Microscopy, Rat
References
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2. Kowluru RA. Diabetic retinopathy, metabolic memory and epigenetic modifications. Vision Res 2017;139:30–38.
3. Sohn EH, van Dijk HW, Jiao C, Kok PH, Jeong W, Demirkaya N, et al. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci US A2016;113:E2655–E2664.
4. Verma A, Raman R, Vaitheeswaran K, Pal SS, Laxmi G, Gupta M, et al. Does neuronal damage precede vascular damage in subjects with type 2 diabetes mellitus and having no clinical diabetic retinopathy? Ophthalmic Res 2012;47:202–207.
5. Park SH, Park JW, Park SJ, Kim KY, Chung JW, Chun MH, et al. Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina. Diabetologia 2003;46:1260–1268.
6. Aiello LM. Perspectives on diabetic retinopathy. Am J Opthalmol 2003;136:122–135.
7. Franconi F, Di Leo MA, Bennardini F, Ghirlanda G. Is taurine beneficial in reducing risk factors for diabetes mellitus? Neurochem Res 2004;29:143–150.
8. Rosenlund BL. Effects of insulin on free amino acids in plasma and the role of the amino acid metabolism in the etiology of diabetic microangiopathy. Biochem Med Metab Biol 1993;49:375–391.
9. Sulochana K, Punitham R, Ramakrishnan S. Beneficial effect of lysine and amino acids on cataractogenesis in experimental diabetes through possible antiglycation of lens proteins. Exp Eye Res 1998;67:597–601.
10. Sulochana KN, Indra C, Rajesh M, Srinivasan V, Ramakrishnan S. Beneficial role of amino acids in mitigating cytoskeletal actin glycation and improving F-actin content: in vitro. Glycoconj J 2001;18:277–282.
11. Pérez-Torres I, María Zuniga-Munoz A, Guarner-Lans V. Beneficial effects of the amino acid glycine. Mini Rev Med Chem 2017;17:15–32.
12. McCarty MF, O’Keefe JH, DiNicolantonio JJ. Dietary glycine is rate-limiting for glutathione synthesis and may have broad potential for health protection. Ochsner J 2018;18:81–87.
13. Adamis AP. Is diabetic retinopathy an inflammatory disease? Br J Ophthalmol 2002;86:363–365.
14. Cruz M, Maldonado-Bernal C, Mondragon-Gonzalez R, Sanchez-Barrera R, Wacher N, Carvajal-Sandoval G, et al. Glycine treatment decreases proinflammatory cytokines and increases interferon-γ in patients with Type 2 diabetes. J Endocrinol Invest 2008;31:694–699.
15. Alvarado-Vasquez N, Lascurain R, Ceron E, Vanda B, Carvajal-Sandoval G, Tapia A, et al. Oral glycine administration attenuates diabetic complications in streptozotocininduced diabetic rats. Life Sci 2006;79:225–232.
16. Alvarado-Vásquez N, Zamudio P, Cerón E, Vanda B, Zenteno E, Carvajal-Sandoval G. effect of glycine in streptozotocin-induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol 2003;134:521–527.
17. Bahmani F, Bathaie SZ, Aldavood SJ, Ghahghaei A. Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. Molvis 2012;18:439.
18. Ramakrishnan S, Sulochana KN. Decrease in glycation of lens proteins by lysine and glycine by scavenging of glucose and possible mitigation of cataractogenesis. Exp Eye Res 1993;57:623–628.
19. Anuradha CV. Aminoacid support in the prevention of diabetes and diabetic complications. Curr Protein Pept Sci 2009;10:8–17.
20. Stitt A, Gardiner T, Archer D. Histological and ultrastructural investigation of retinal microaneurysm development in diabetic patients. Br J Ophthalmol 1995;79:362–367.
21. Ishibashi T, Inomata H. Ultrastructure of retinal vessels in diabetic patients. Br J Ophthalmol 1993;77:574–578.
22. Van Dijk HW, Verbraak FD, Kok PH, Stehouwer M, Garvin MK, Sonka M, et al. Early neurodegeneration in the retina of type 2 diabetic patients retinal neurodegeneration in type 2 diabetes. Invest Ophthalmol Vis Science 2012;53:2715–2719.
23. Mizutani M, Gerhardinger C, Lorenzi M. Müller cell changes in human diabetic retinopathy. Diabetes1998;47:445–449.
24. Bringmann A, Pannicke T, Grosche J, Francke M, Wiedemann P, Skatchkov SN, et al. Muller cells in the healthy and diseased retina. Prog Retin Eye Res 2006;25:397–424.
25. Fletcher EL, Phipps JA, Wilkinson‐Berka JL. Dysfunction of retinal neurons and glia during diabetes. Clin Exp Optom 2005;88:132–145.
26. Baydas G, Tuzcu M, Yasar A, Baydas B. Early changes in glial reactivity and lipid peroxidation in diabetic rat retina: effects of melatonin. Actadiabetologica 2004;41:123–128.
27. Barile GR, Pachydaki SI, Tari SR, Lee SE, Donmoyer CM, Ma W, et al. The RAGE axis in early diabetic retinopathy. Invest Ophthalmol Vis Science 2005;46:2916–2924.
28. Guidry C. The role of Müller cells in fibrocontractive retinal disorders. Prog Retin Eye Res 2005;24:75–86.
29. Young RW. The renewal of photoreceptor cell outer segments. J Cell Biol 1967;33:61–72.
30. Young RW, Bok D. Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol 1969;42:392–403.
31. Rajala A, Dighe R, Agbaga M-P, Anderson RE, Rajala RV. Insulin receptor signaling in cones. J Biol Chem 2013;288:19503–19515.
32. Reiter CE, Wu X, Sandirasegarane L, Nakamura M, Gilbert KA, Singh RS, et al. Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin. Diabetes 2006;55:1148–1156.
33. Kern TS, Barber AJ. Retinal ganglion cells in diabetes. J Physiol 2008;586:4401–4408.
34. Gannon MC, Nuttall JA, Nuttall FQ. The metabolic response to ingested glycine. Am J Clin Nutr 2002;76:1302–1307.
35. Kowluru RA, Kowluru A, Veluthakal R, Mohammad G, Syed I, Santos JM, et al. TIAM1–RAC1 signalling axis-mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia 2014;57:1047–1056.
36. Behl T, Kaur I, Kotwani A. Implication of oxidative stress in progression of diabetic retinopathy. Surv Ophthalmol 2016;61:187–196.
2. Kowluru RA. Diabetic retinopathy, metabolic memory and epigenetic modifications. Vision Res 2017;139:30–38.
3. Sohn EH, van Dijk HW, Jiao C, Kok PH, Jeong W, Demirkaya N, et al. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci US A2016;113:E2655–E2664.
4. Verma A, Raman R, Vaitheeswaran K, Pal SS, Laxmi G, Gupta M, et al. Does neuronal damage precede vascular damage in subjects with type 2 diabetes mellitus and having no clinical diabetic retinopathy? Ophthalmic Res 2012;47:202–207.
5. Park SH, Park JW, Park SJ, Kim KY, Chung JW, Chun MH, et al. Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina. Diabetologia 2003;46:1260–1268.
6. Aiello LM. Perspectives on diabetic retinopathy. Am J Opthalmol 2003;136:122–135.
7. Franconi F, Di Leo MA, Bennardini F, Ghirlanda G. Is taurine beneficial in reducing risk factors for diabetes mellitus? Neurochem Res 2004;29:143–150.
8. Rosenlund BL. Effects of insulin on free amino acids in plasma and the role of the amino acid metabolism in the etiology of diabetic microangiopathy. Biochem Med Metab Biol 1993;49:375–391.
9. Sulochana K, Punitham R, Ramakrishnan S. Beneficial effect of lysine and amino acids on cataractogenesis in experimental diabetes through possible antiglycation of lens proteins. Exp Eye Res 1998;67:597–601.
10. Sulochana KN, Indra C, Rajesh M, Srinivasan V, Ramakrishnan S. Beneficial role of amino acids in mitigating cytoskeletal actin glycation and improving F-actin content: in vitro. Glycoconj J 2001;18:277–282.
11. Pérez-Torres I, María Zuniga-Munoz A, Guarner-Lans V. Beneficial effects of the amino acid glycine. Mini Rev Med Chem 2017;17:15–32.
12. McCarty MF, O’Keefe JH, DiNicolantonio JJ. Dietary glycine is rate-limiting for glutathione synthesis and may have broad potential for health protection. Ochsner J 2018;18:81–87.
13. Adamis AP. Is diabetic retinopathy an inflammatory disease? Br J Ophthalmol 2002;86:363–365.
14. Cruz M, Maldonado-Bernal C, Mondragon-Gonzalez R, Sanchez-Barrera R, Wacher N, Carvajal-Sandoval G, et al. Glycine treatment decreases proinflammatory cytokines and increases interferon-γ in patients with Type 2 diabetes. J Endocrinol Invest 2008;31:694–699.
15. Alvarado-Vasquez N, Lascurain R, Ceron E, Vanda B, Carvajal-Sandoval G, Tapia A, et al. Oral glycine administration attenuates diabetic complications in streptozotocininduced diabetic rats. Life Sci 2006;79:225–232.
16. Alvarado-Vásquez N, Zamudio P, Cerón E, Vanda B, Zenteno E, Carvajal-Sandoval G. effect of glycine in streptozotocin-induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol 2003;134:521–527.
17. Bahmani F, Bathaie SZ, Aldavood SJ, Ghahghaei A. Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. Molvis 2012;18:439.
18. Ramakrishnan S, Sulochana KN. Decrease in glycation of lens proteins by lysine and glycine by scavenging of glucose and possible mitigation of cataractogenesis. Exp Eye Res 1993;57:623–628.
19. Anuradha CV. Aminoacid support in the prevention of diabetes and diabetic complications. Curr Protein Pept Sci 2009;10:8–17.
20. Stitt A, Gardiner T, Archer D. Histological and ultrastructural investigation of retinal microaneurysm development in diabetic patients. Br J Ophthalmol 1995;79:362–367.
21. Ishibashi T, Inomata H. Ultrastructure of retinal vessels in diabetic patients. Br J Ophthalmol 1993;77:574–578.
22. Van Dijk HW, Verbraak FD, Kok PH, Stehouwer M, Garvin MK, Sonka M, et al. Early neurodegeneration in the retina of type 2 diabetic patients retinal neurodegeneration in type 2 diabetes. Invest Ophthalmol Vis Science 2012;53:2715–2719.
23. Mizutani M, Gerhardinger C, Lorenzi M. Müller cell changes in human diabetic retinopathy. Diabetes1998;47:445–449.
24. Bringmann A, Pannicke T, Grosche J, Francke M, Wiedemann P, Skatchkov SN, et al. Muller cells in the healthy and diseased retina. Prog Retin Eye Res 2006;25:397–424.
25. Fletcher EL, Phipps JA, Wilkinson‐Berka JL. Dysfunction of retinal neurons and glia during diabetes. Clin Exp Optom 2005;88:132–145.
26. Baydas G, Tuzcu M, Yasar A, Baydas B. Early changes in glial reactivity and lipid peroxidation in diabetic rat retina: effects of melatonin. Actadiabetologica 2004;41:123–128.
27. Barile GR, Pachydaki SI, Tari SR, Lee SE, Donmoyer CM, Ma W, et al. The RAGE axis in early diabetic retinopathy. Invest Ophthalmol Vis Science 2005;46:2916–2924.
28. Guidry C. The role of Müller cells in fibrocontractive retinal disorders. Prog Retin Eye Res 2005;24:75–86.
29. Young RW. The renewal of photoreceptor cell outer segments. J Cell Biol 1967;33:61–72.
30. Young RW, Bok D. Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol 1969;42:392–403.
31. Rajala A, Dighe R, Agbaga M-P, Anderson RE, Rajala RV. Insulin receptor signaling in cones. J Biol Chem 2013;288:19503–19515.
32. Reiter CE, Wu X, Sandirasegarane L, Nakamura M, Gilbert KA, Singh RS, et al. Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin. Diabetes 2006;55:1148–1156.
33. Kern TS, Barber AJ. Retinal ganglion cells in diabetes. J Physiol 2008;586:4401–4408.
34. Gannon MC, Nuttall JA, Nuttall FQ. The metabolic response to ingested glycine. Am J Clin Nutr 2002;76:1302–1307.
35. Kowluru RA, Kowluru A, Veluthakal R, Mohammad G, Syed I, Santos JM, et al. TIAM1–RAC1 signalling axis-mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia 2014;57:1047–1056.
36. Behl T, Kaur I, Kotwani A. Implication of oxidative stress in progression of diabetic retinopathy. Surv Ophthalmol 2016;61:187–196.