Effects of hydralazine on NaIO3-induced rat retinal pigment epithelium degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

ABSTRACT

·AIM: To study the effects of 10g/L hydralazine eye drops on 35mg/kg NaIO3-induced degeneration in rat eyes. · METHODS: Various doses of NalO3 and/or saline alone were injected into Brown Norway rats from hypoglossal vein. After 3, 7, 14 or 28 days of injection, ERG a-, b-, c- wave, fast oscillation (FO) and light peak (LP) were measured along with retinal colored pictures and fluorescein angiography taken. Some rats were chosen to study the histology of retinas by light microscopy and autofluorescence of retina flatmounts. Different concen- trations of NaIO3 were given to RPE-19 cells, and cell proliferation rate was measured. For hydralazine study, 35mg/kg NaIO3 was injected into Brown Norway rat from hypoglossal vein. NaIO3 group was treated with saline alone after NaIO3 injection, 10g/L hydralazine + NaIO3 group was treated with 10g/L hydralazine eyedrops after NaIO3 injection whereas normal group was treated with saline alone without NalO3 injection. All eyedrops were instilled locally 3 times a day for 4 weeks and ERG c-wave was measured at the end of 2 and 4 weeks.· RESULTS: After NaIO3 administration, the amplitude of all ERG waves fell markedly in large dose groups at 30, 40 or 60mg/kg NaIO3. Not many changes were observed in groups treated with < 30mg/kg NaIO3. Some retinal necrosis appeared from 3 days post-injection (PI) in 30mg/kg NaIO3 group, which became more serious in larger dose groups or longer treatment time, but no apparent change was found in smaller dose groups. Similarly, on the retina flatmount, RPE monolayer showed necrosis from 3 days PI in the 30mg/kg NaIO3 and larger dose groups. On histological examination, no significant change was seen in 30mg/kg NaIO3 and lower concentration groups. In cell culture experiment, changes were found in RPE-19 cells proliferation rate with a concentration of NaIO3 at 30mg/L or higher. In hydralazine experiments, 4 weeks after injection of NaIO3, ERG c-wave fell markedly in NaIO3 group to 31% of control group (P < 0.01). The ERG c-wave of hydra- lazine + NaIO3 group fell only to 50% of control group (P<0.05). This was a 61% reversal of the c-wave of NaIO3 treated group. · CONCLUSION: RPE degeneration induced by NaIO3 was both dose and time dependent. Around 30 to 40 mg/kg NaIO3 would be the optimal to be used as a non-exudative age-related macular degeneration rat model. Hydralazine may postpone the development of non-exudative age- related macular degeneration.