Effects of minocycline on experimental retinal degeneration induced by n-methyl-n-nitrosourea in rats

Retinal degeneration (RD) is often associated with deficiencies or inaccurate production of photoreceptor-specific proteins encoded by various genes, characterized by apoptotic and ongoing death of photoreceptor cells. In this study, 80 rats were given a single dose of intraperitoneally (i.p.) 50 mg / kg N-Methyl-N-Nitrosourea (MNU) to induce RD. Sixty of these rats were treated with i.p. minocycline, at different doses (50 mg/kg: 20 animals, 75 mg/kg: 20 animals, 100 mg/kg: 20 animals) and two times; 1 day before and 1 hour later of MNU administration, to prevent retinal degeneration. Twenty animals were administered only saline, as control animals. Euthanasia was performed in 5 different periods, at 12th, 24th, 48th, 72th hours and 7th day, during the seven-day experiment, and eye samples were obtained. Eye samples were examined histopathologically, immunohistochemically and electron microscopically. Significant RD was observed in MNU-administered groups, and photoreceptor deaths were demonstrated by the TUNEL method, which was performed by apoptotic mechanism. Compared to the control group, without MNU administration, it was seen that photoreceptor layer and outer nuclear layer gradually become thinner and increased levels of caspase-3, caspase-6, bax, 8-OHdG, PCNA, GFAP and decreased levels of rhodopsin, red/green opsin and Bcl-2, starting from the 12th hour. Electron microscopic studies showed that amacrin and bipolar cells were also affected but not only by the size of the photoreceptors. There was no significant difference in treatment groups treated with minocycline, and it was seen that minocycline is ineffective on retinal layer thicknesses and staining levels of caspase-3, caspase-6, bax, 8-OHdG, PCNA, GFAP, rhodopsin, red / green opsin and Bcl-2 in MNU-induced retinal degeneration. Consequently, it has been determined that MNU affects a large number of photoreceptor cells in a short time with a single dose application, while minocycline has been shown to be ineffective to prevent this condition. It is thought that this would require investigating the efficacy of minocycline with different combinations of drugs, due to the large number of factors involved in the pathogenesis of MNU-induced RD.