Comparative Clinical Pathology

, Volume 28, Issue 1, pp 89–95 | Cite as

Protective effects of curcumin on ischemic reperfusion of rat retina

  • Arash EsfandiariEmail author
  • Farid Hashemi
Original Article



Ischemic reperfusion is an optic neuropathy in which photoreceptor cells may die through an apoptotic process. Free radicals are involved in the apoptotic process of ischemic reperfusion disorders. Previous research indicates that curcumin is an antioxidant found in plants which reduces neurodegenerative changes in aged animals.


The purpose of this research was to survey whether curcumin has preventive effects on ischemic reperfusion of the retina.


Twenty male Wistar rats were grouped into four (n = 5): 1, control group; 2, ischemic reperfusion group; 3, experimental group II: received 0.01% curcumin in diet (low dose) for 2 days before ischemic reperfusion; 4, experimental group III: received 0.25% curcumin in diet (high dose) for 2 days before ischemic reperfusion. The eye was enucleated and the retina separated. Routine tissue processing in transmission electron microscopy was done.


Results showed that ischemic reperfusion created major signs of injury in the photoreceptor layer such as disappearance of the outer segment, cell swelling, and karyolitic and pyknotic nuclei, but cell swelling and karyolitic nuclei were not seen after receiving a low dose of curcumin. Also, the photoreceptor layer appeared normal after receiving a high dose of curcumin, but decreased vacuolization and dark and inactive nuclei were obvious.


This study concluded that a high dose of curcumin confers a more preventive effect on retinal injury by ischemic reperfusion than a low dose.


Ischemic reperfusion Photoreceptor cell Curcumin Transmission electron microscopy Rat 



The authors thank Ali Safavi for assistance with electron microscope technique.

Funding information

This study was conducted under the sponsorship of the Kazerun Branch, Islamic Azad University, Kazerun, Iran.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This study followed all the guidelines for the care and use animals.


  1. Agardh CD, Gustavsson C, Hagert P, Nilsson M, Agardh E (2006) Expression of antioxidant enzymes in rat retinal ischemia followed by reperfusion. Metab 55:892–898. CrossRefGoogle Scholar
  2. Aldebasi YH, Aly SM, Rahmani AH (2013) Therapeutic implications of curcumin in the prevention of diabetic retinopathy via modulation of anti-oxidant activity and genetic pathway. Int J Physiol Pathophysiol Pharmacol 5:194–202Google Scholar
  3. Aliabadi A, Esfandiari A, Rajaei R (2016) Transmission electron microscopy of the retina following thyroidectomy in rabbit. Comp Clin Pathol 25(2):265–269. CrossRefGoogle Scholar
  4. Anna K, Mammis JA, Savitz SI et al (2002) Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. PNAS 99(16):10659–10664. CrossRefGoogle Scholar
  5. Baudouin C, Pisella PJ, Ettaiche M, Goldschild M, Becquet F, Gastaud P (1999) Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical. Graefes Arch Clin Exp Ophthalmol 237:58–66CrossRefGoogle Scholar
  6. Bonne C, Muller A, Villain M (1998) Free radicals in retinal ischemia. Gen Pharmacol 30:275–280CrossRefGoogle Scholar
  7. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate and neurodegenerative disorders. Science 262:689–695CrossRefGoogle Scholar
  8. Dilsiz N, Sahaboglu A, Yildiz MZ, Reichenbach A (2006) Protective effects of various antioxidants during ischemia-reperfusion in the rat retina. Graefes Arch Clin Exp Ophthalmol 244:627–633. CrossRefGoogle Scholar
  9. Esfandiari A, Yousofi AR, Dehghan A, Safavi A (2009) Effect of intermittent light on photoreceptor cells in the rabbit retina. Jpn J Ophthalmol 53:635–639. CrossRefGoogle Scholar
  10. Flammer J, Orgül S (1998) Optic nerve blood-flow abnormalities in glaucoma. Prog Retin Eye Res 17:267–289CrossRefGoogle Scholar
  11. Fox NE, van Kuijk FJ (1998) Immunohistochemical localization of xanthine oxidase in human retina. Free Radic Biol Med 24:900–905CrossRefGoogle Scholar
  12. Guo L, Moss SE, Alexander RA, Ali RR, Fitzke FW, Cordeiro MF (2005) Retinal ganglion cell apoptosis in glaucoma is related to intraocular pressure and IOP induced effects on extracellular matrix. Invest Ophthalmol Vis Sci 46:175–182. CrossRefGoogle Scholar
  13. Hardy P, Beauchamp M, Sennlaub F et al (2005) New insights into the retinal circulation: inflammatory lipid mediators in ischemic retinopathy. Prostaglandins Leukot Essent Fatty Acids 72:301–325. CrossRefGoogle Scholar
  14. Jo N, Wu GS, Rao NA (2003) Up regulation of chemokine expression in the retinal vasculature in ischemia-reperfusion injury. Invest Ophthalmol Vis Sci 44:4054–4060CrossRefGoogle Scholar
  15. Leinonen JS, Ahonen JP, Lonnrot K et al (2000) Low plasma antioxidant activity is associated with high lesion volume and neurological impairment in stroke. Stroke 31:33–39CrossRefGoogle Scholar
  16. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  17. Mallick IH, Yang W, Winslet MC, Seifalian AM (2004) Ischemia-reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 49:1359–1377CrossRefGoogle Scholar
  18. Moreno MC, Campanelli J, Sande P, Sánez DA et al (2004) Retinal oxidative stress induced by high intraocullar pressure. Free Radic Biol Med 37(6):803–812CrossRefGoogle Scholar
  19. Nakashima M, Niwa M, Iwai T, Uematsu T (1999) Involvement of free radicals in cerebral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat. Free Radic Biol Med 26:722–729CrossRefGoogle Scholar
  20. Okamoto T, Yamagishi S, Inagaki Y, Amano S et al (2002) Angiogenesis induced by advanced glycation and products and prevention by cerivastatin. FASEB 16:1928–1930. CrossRefGoogle Scholar
  21. Osawa T, Kato Y (2005) Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann N Y Acad Sci 1043:440–451. CrossRefGoogle Scholar
  22. Osborne NN, Casson RJ, Wood JP, Chidlow G et al (2004) Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res 23:91–147. CrossRefGoogle Scholar
  23. Oz O, Gürelik G, Akyürek N, Cinel L et al (2005) A short duration transient ischemia induces apoptosis in retinal layers: an experimental study in rabbits. Eur J Ophthalmol 15:233–238CrossRefGoogle Scholar
  24. Patricia VT (2008) The Calam/Acmal Standards of Veterinary Care and laboratory animal welfare. Can Vet J 49:86–88Google Scholar
  25. Peddada KV, Brown A, Verma V, Nebbioso M (2018) Therapeutic potential of curcumin in major retinal pathologies. Int Ophthalmol 2018.
  26. Rosenbaum DM, Rosenbaum PS, Singh M, Gupta G, Gupta H, Li B, Roth S (2001) Functional and morphologic comparison of two methods to produce transient retinal ischemia in the rat. J Neuroophthalmol 21:62–68CrossRefGoogle Scholar
  27. Sakamoto K, Yonoki Y, Kuwagata M, Saito M, Nakahara T, Ishii K (2004) Histological protection against ischemia-reperfusion injury by early ischemic preconditioning in rat retina. Brain Res 1015:154–160. CrossRefGoogle Scholar
  28. Sanchez RN, Chan CK, Garg S, Kwong JMK, Wong MJ, Sadun AA, Lam TT (2003) Interleukin-6 in retinal ischemia reperfusion injury in rats. Invest Ophthalmol Vis Sci 44:4006–4011CrossRefGoogle Scholar
  29. Srinivasan M (1972) Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 26:269–270Google Scholar
  30. Strasser EM, Wessner B, Manhart N, Roth E (2005) The relationship between the anti-inflammatory effects of curcumin and cellular gluthatione content in myelomonocytic cells. Biochem Pharmacol 70:552–559. CrossRefGoogle Scholar
  31. Sugawara T, Chan PH (2003) Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid Redox Signal 5:597–607. CrossRefGoogle Scholar
  32. Szabo ME, Droy-Lefaix MT, Doly M, Carré C, Braquet P (1991) Ischemia and reperfusion induced histologic changes in the rat retina. Demonstration of a free radical-mediated mechanism. Invest Ophthalmol Vis Sci 32:1471–1478Google Scholar
  33. Thaakur S, Sravanthi R (2010) Neuroprotective effect of Spirulina in cerebral ischemia–reperfusion injury in rats. J Neural Transm 117:1083–1091. CrossRefGoogle Scholar
  34. Wang Y, Chang CF, Chou J, Chen HL, Deng X, Harvey BK, Cadet JL, Bickford PC (2005) Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol 193:75–84. CrossRefGoogle Scholar
  35. Wang L, Li C, Guo H, Kern TS, Huang K, Zheng L (2011) Curcumin inhibits neuronal and vascular degeneration in retina after ischemia and reperfusion injury. PLoS One 6:e23194. CrossRefGoogle Scholar
  36. Warner D, Sheng H, Batinic-Haberle I (2004) Oxidants, antioxidants and the ischemic brain. J Exp Biol 207:3221–3231. CrossRefGoogle Scholar
  37. Yang GY, Pang L, Ge HL, Tan M, Ye W, Liu XH, Huang FP, Wu DC, Che XM, Song Y, Wen R, Sun Y (2001) Attenuation of ischemia-induced mouse brain injury by SAG, a redox-inducible antioxidant protein. J Cereb Blood Flow Metab 21:722–733. CrossRefGoogle Scholar
  38. Zheng L, Gong B, Hatala DA, Kern TS (2007) Retinal ischemia and reperfusion causes capillary degeneration: similarities to diabetes. Invest Ophthalmol Vis Sci 48:361–367. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Basic Sciences of Veterinary Medicine, Kazerun BranchIslamic Azad UniversityKazerunIran
  2. 2.Young Researchers and Elite Club, Kazerun BranchIslamic Azad UniversityKazerunIran

Personalised recommendations