Protection of retinal function by nucleoside reverse transcriptase inhibitors following retinal ischemic-reperfusion injury

Abstract

Purpose : Retinal ischemia is a common cause of visual impairment and blindness for which there remain limited treatment options. Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (AZT), block the NLRP3 inflammasome and prevent retinal degeneration in a mouse model of age-related macular degeneration (AMD). In this study, we investigated the neuroprotective effects of AZT using a pressure-induced retinal ischemic mouse model.

Methods : C57BL/6 mice (8 weeks old) were randomly assigned to one of two groups: vehicle-treated retinal ischemic injury mice (control) or AZT-treated retinal ischemic injury mice. Vehicle (1% DMSO in PBS) or AZT 50 mg/kg in 1% DMSO in PBS was injected intraperitoneally twice daily for 5 days. On the second day of treatment, retinal ischemia was induced by transient elevation of intraocular pressure for 45 minutes. Scotopic electroretinography (ERG) was recorded before AZT or vehicle treatment and 7 days after inducing ischemic retinal injury.

Results : Before treatment, scotopic ERG a- and b-wave amplitudes were an average of 371 ± 75 μV and 701 ± 107 μV, respectively, in the AZT group and 340 ± 50 μV and 635 ± 41 μV, respectively, in the control group. Following ischemic-reperfusion injury, ERG a-wave amplitudes were 93 ± 63 μV in the control group and 249 ± 30 μV in the AZT group (p = 0.018). Post-ischemic insult ERG b-wave amplitudes were 163 ± 96 μV in the control group and 439 ± 83 μV in the AZT group (p = 0.019). Seven days after ischemic-reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in vehicle-treated mice, whereas AZT treatment attenuated ischemic induced loss of retinal function as compared to that seen in vehicle-treated mice.

Conclusions : AZT treatment of mice improved ERG a-wave and b-wave amplitudes following ischemic insult as compared to those seen in controls. Our preliminary findings suggest that AZT may have therapeutic value in the management of retinal ischemic diseases.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.