Vet Med - Czech, 2025, 70(7):247-260 | DOI: 10.17221/122/2024-VETMED
Exploring minocycline’s effect on retinal degeneration following N-methyl-N-nitrosourea exposure in ratsOriginal Paper
- 1 Department of Pathology, Veterinary Faculty, Firat University, Elazig, Turkiye
- 2 Department of Histology, Medicine School, Inonu University, Malatya, Turkiye
Retinal degeneration (RD) is often associated with deficiencies or the inaccurate production of photoreceptor-specific proteins, which are encoded by various genes and characterised by the apoptotic and ongoing death of photoreceptor cells. This study involved administering a single intraperitoneal (i.p.) dose of 50 mg/kg of N-methyl-N-nitrosourea (MNU) to rats to induce RD. Some of these rats also received intraperitoneal minocycline at varying doses to prevent RD. Euthanasia was conducted at five intervals: at 12, 24, 48, and 72 h, and on the 7th day; and eye samples were taken. These samples were analysed using histopathology, immunohistochemistry, and electron microscopy. Significant RD was observed in the MNU-treated groups, with photoreceptor cell apoptosis demonstrated by the TUNEL method. Compared with those in the control group, there was a progressive thinning of the photoreceptor layer and outer nuclear layer, along with increased levels of glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA), and reduced levels of rhodopsin and red/green opsin starting from the 12th hour in the experimental groups. Electron microscopy revealed that amacrine and bipolar cells, in addition to photoreceptors, were also affected. The minocycline treatment did not show significant differences in retinal layer thickness or the staining levels of PCNA, GFAP, and opsins in the MNU-induced RD model.
Keywords: minocycline; retinal degeneration; retinitis pigmentosa
Received: December 23, 2024; Revised: May 14, 2025; Accepted: May 22, 2025; Prepublished online: July 25, 2025; Published: July 29, 2025 Show citation
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References
- Aplin FP, Luu CD, Vessey KA, Guymer RH, Shepherd RK, Fletcher EL. ATP-induced photoreceptor death in a feline model of retinal degeneration. Invest Ophthalmol Vis Sci. 2014 Nov 25;55(12):8319-29.
Go to original source...
Go to PubMed...
- Bonelli RM, Heuberger C, Reisecker F. Minocycline for Huntington's disease: An open label study. Neurology. 2003 Mar 11;60(5):883-4.
Go to original source...
Go to PubMed...
- Carter JH, Douglass LE, Deddens JA, Colligan BM, Bhatt TR, Pemberton JO, Konicek S, Hom J, Marshall M, Graff JR. Pak-1 expression increases with progression of colorectal carcinomas to metastasis. Clin Cancer Res. 2004 May 15;10(10):3448-56.
Go to original source...
Go to PubMed...
- Chang CJ, Cherng CH, Liou WS, Liao CL. Minocycline partially inhibits caspase-3 activation and photoreceptor degeneration after photic injury. Ophthalmic Res. 2005 Jul-Aug;37(4):202-13.
Go to original source...
Go to PubMed...
- Danulescu R, Costin D. Use of blood markers in early diagnosis of oxidative stress in age related macular degeneration. Rev Med Chir Soc Med Nat Iasi. 2012 Oct-Dec;116(4):1136-42.
- Du X, Byrne EM, Chen M, Xu H. Minocycline inhibits microglial activation and improves visual function in a chronic model of age-related retinal degeneration. Biomedicines. 2022 Dec 12;10(12):3222.
Go to original source...
Go to PubMed...
- Emoto Y, Yoshizawa K, Kinoshita Y, Yuri T, Yuki M, Sayama K, Shikata N, Tsubura A. Green tea extract suppresses N-methyl-N-nitrosourea-induced photoreceptor apoptosis in Sprague-Dawley rats. Graefes Arch Clin Exp Ophthalmol. 2014 Sep;252(9):1377-84.
Go to original source...
Go to PubMed...
- Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010 Mar 19;140(6):918-34.
Go to original source...
Go to PubMed...
- He J, Mao J, Hou L, Jin S, Wang X, Ding Z, Jin Z, Guo H, Dai R. Minocycline attenuates neuronal apoptosis and improves motor function after traumatic brain injury in rats. Exp Anim. 2021 Nov 10;70(4):563-9.
Go to original source...
Go to PubMed...
- Hsu SM, Raine L, Fanger H. The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am J Clin Pathol. 1981 Jun;75(6):816-21.
Go to original source...
Go to PubMed...
- Jing H, Nie M, Wang X, Zhang Z, Xu Y, Zhang G, Li D, Dai Z. Lutein combined with EGCG improved retinitis pigmentosa against N-methyl-N nitrosourea-induced. Food Funct. 2023 Oct 30;14(21):9554-66.
Go to original source...
Go to PubMed...
- Grotegut P, Perumal N, Kuehn S, Smit A, Dick HB, Grus FH, Joachim SC. Minocycline reduces inflammatory response and cell death in a S100B retina degeneration model. J Neuroinflammation. 2020 Dec 14;17(1):375.
Go to original source...
Go to PubMed...
- Kiuchi K, Kondo M, Ueno S, Moriguchi K, Yoshizawa K, Miyake Y, Matsumura M, Tsubura A. Functional rescue of N-methyl-N-nitrosourea-induced retinopathy by nicotinamide in Sprague-Dawley rats. Curr Eye Res. 2003 Jun;26(6):355-62.
Go to original source...
Go to PubMed...
- Koriyama Y, Sugitani K, Ogai K, Kato S. Heat shock protein 70 induction by valproic acid delays photoreceptor cell death by N-methyl-N-nitrosourea in mice. J Neurochem. 2014 Sep;130(5):707-19.
Go to original source...
Go to PubMed...
- Kosec G, Kafarnik C, Sayers G, Scurrell EJ, Carter WJ. Outer retinal degeneration in two closely related Goeldi's monkeys (Callimico goeldii). Vet Ophthalmol. 2020 Mar;23(2):394-401.
Go to original source...
Go to PubMed...
- Kuro M, Yoshizawa K, Uehara N, Miki H, Takahashi K, Tsubura A. Calpain inhibition restores basal autophagy and suppresses MNU-induced photoreceptor cell death in mice. In Vivo. 2011 Jul-Aug;25(4):617-23.
- Langmann T. Microglia activation in retinal degeneration. J Leukoc Biol. 2007 Jun;81(6):1345-51.
Go to original source...
Go to PubMed...
- Lynch AM, Ruterbories LK, Robertson JB, Lunn KF, Mowat FM. Hemostatic profiles in dogs with sudden acquired retinal degeneration syndrome. J Vet Intern Med. 2023 May-Jun;37(3):948-59.
Go to original source...
Go to PubMed...
- McKay JS, Steele SJ, Ahmed G, Johnson E, Ratcliffe K. An antibody panel for immunohistochemical analysis of the retina in Davidson's-fixed, paraffin-embedded eyes of rats. Exp Toxicol Pathol. 2009 Mar;61(2):91-100.
Go to original source...
Go to PubMed...
- Minella AL, Occelli LM, Narfstrom K, Petersen-Jones SM. Central retinal preservation in rdAc cats. Vet Ophthalmol. 2018 May;21(3):224-32.
Go to original source...
Go to PubMed...
- Ogino H, Ito M, Matsumoto K, Yagyu S, Tsuda H, Hirono I, Wild CP, Montesano R. Retinal degeneration induced by N-methyl-N-nitrosourea and detection of 7-methyldeoxyguanosine in the rat retina. Toxicol Pathol. 1993;21(1):21-5.
Go to original source...
Go to PubMed...
- Ozaki E, Delaney C, Campbell M, Doyle SL. Minocycline suppresses disease-associated microglia (DAM) in a model of photoreceptor cell degeneration. Exp Eye Res. 2022 Apr;217:108953.
Go to original source...
Go to PubMed...
- Peng B, Xiao J, Wang K, So KF, Tipoe GL, Lin B. Suppression of microglial activation is neuroprotective in a mouse model of human retinitis pigmentosa. J Neurosci. 2014 Jun 11;34(24):8139-50.
Go to original source...
Go to PubMed...
- Reisenhofer M, Balmer J, Zulliger R, Enzmann V. Multiple programmed cell death pathways are involved in N-methyl-N-nitrosourea-induced photoreceptor degeneration. Graefes Arch Clin Exp Ophthalmol. 2015 May;253(5):721-31.
Go to original source...
Go to PubMed...
- Shi E, Wang X, Jing H, Xu Y, Feng L, He F, Li D, Dai Z. Synergistic effect of chitosan and β-carotene in inhibiting MNU-induced retinitis pigmentosa. Int J Biol Macromol. 2024 May;268(Pt 2):131671.
Go to original source...
Go to PubMed...
- Sivaprasad S, Patra S, DaCosta J, Adewoyin T, Shona O, Pearce E, Chong NV. A pilot study on the combination treatment of reduced-fluence photodynamic therapy, intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for neovascular age-related macular degeneration. Ophtalmologica. 2011;225(4):200-6.
Go to original source...
Go to PubMed...
- Sun Y, Sun Y, Chen S, Yu Y, Ma Y, Sun F. Hypoxic preconditioned MSCs-derived small extracellular vesicles for photoreceptor protection in retinal degeneration. J Nanobiotechnology. 2023 Nov 25;21(1):449.
Go to original source...
Go to PubMed...
- Tappeiner C, Balmer J, Iglicki M, Schuerch K, Jazwinska A, Enzmann V, Tschopp M. Characteristics of rod regeneration in a novel zebrafish retinal degeneration model using N-methyl-N-nitrosourea (MNU). PLoS One. 2013 Aug 12;8(8):e71064.
Go to original source...
Go to PubMed...
- Terauchi R, Kohno H, Watanabe S, Saito S, Watanabe A, Nakano T. Minocycline decreases CCR2-positive monocytes in the retina and ameliorates photoreceptor degeneration in a mouse model of retinitis pigmentosa. PLoS One. 2021 Apr 22;16(4):e0239108.
Go to original source...
Go to PubMed...
- Thomas M, Le WD, Jankovic J. Minocycline and other tetracycline derivatives: A neuroprotective strategy in Parkinson's disease and Huntington's disease. Clin Neuropharmacol. 2003 Jan-Feb;26(1):18-23.
Go to original source...
Go to PubMed...
- Tsubara A, Yoshizawa K, Kuro M. N-Methyl-N-nitrosourea animal models for retinitis pigmentosa. In: Conn M, editor. Animal models for the study of human disease. Animal models for the study of human disease. Amsterdam, Netherlands: Elsevier Inc.; 2007. p. 117-44.
Go to original source...
- Xu H, Yang JN, Li XK, Zheng Q, Zhao W, Su ZJ, Huang YD. Retina protective effect of acidic fibroblast growth factor after canceling its mitogenic activity. J Ocul Pharmacol Ther. 2008 Oct;24(5):445-51.
Go to original source...
Go to PubMed...
- Yan W, He Q, Long P, Zhang L, Wang H, Chen T. A novelly-spatiotemporal characterization of the disease course in the MNU-induced retinitis pigmentosa model. J Inflamm Res. 2024 Nov 20;17:9243-54.
Go to original source...
Go to PubMed...
- Yang L, Kim JH, Kovacs KD, Arroyo JG, Chen DF. Minocycline inhibition of photoreceptor degeneration. Arch Ophthalmol. 2009 Nov;127(11):1475-80.
Go to original source...
Go to PubMed...
- Yoshizawa K, Nambu H, Yang J, Oishi Y, Senzaki H, Shikata N, Miki H, Tsubura A. Mechanisms of photoreceptor cell apoptosis induced by N-methyl-N-nitrosourea in Sprague-Dawley rats. Lab Invest. 1999 Nov;79(11):1359-67.
- Zhang C, Lei B, Lam TT, Yang F, Sinha D, Tso MO. Neuroprotection of photoreceptors by minocycline in light-induced retinal degeneration. Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2753-9.
Go to original source...
Go to PubMed...
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