PMID- 34448620 OWN - NLM STAT- MEDLINE DCOM- 20220121 LR - 20220121 IS - 1557-7732 (Electronic) IS - 1080-7683 (Linking) VI - 37 IP - 8 DP - 2021 Oct TI - Protection of Retinal Function by Nucleoside Reverse Transcriptase Inhibitors Following Retinal Ischemia/Reperfusion Injury. PG - 485-491 LID - 10.1089/jop.2020.0083 [doi] AB - Purpose: Retinal ischemia/reperfusion (I/R) injury 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), have been shown to block the NLRP3 inflammasome and prevent retinal degeneration in a mouse model of age-related macular degeneration. The NLRP3 inflammasome has also been shown to be triggered in I/R injury. Therefore, we studied the neuroprotective effects of AZT using a pressure-induced retinal ischemia mouse model. Methods: C57BL/6J mice were randomly assigned to 1 of 2 treatment groups: vehicle-treated retinal I/R injury (n = 6) or AZT-treated retinal I/R injury (n = 6). Vehicle (1% dimethyl sulfoxide [DMSO] in phosphate-buffered saline [PBS]) or AZT 50 mg/kg in 1% DMSO in PBS were injected intraperitoneally twice daily for 5 days. On day 2 of treatment, retinal ischemia was induced by transient elevation of intraocular pressure for 45 min. Scotopic electroretinography (ERG) was used to quantify retinal function before and 1 week after retinal ischemic insult. Retinal morphology was examined 1 week after ischemic insult. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays and caspase 1 immunostaining was performed 24 h after retinal I/R injury. Results: Following I/R injury, ERG a- and b-wave amplitudes were significantly reduced in the vehicle-treated mice. AZT treatment significantly attenuated I/R-induced loss of retinal function as compared with vehicle-treated mice. Additionally, AZT-treated mice experienced significantly less inner retinal thinning as compared with vehicle-treated mice. TUNEL-positive cells were prevalent in the vehicle-treated I/R injury mouse retinas compared with the AZT-treated I/R injury mouse retinas. More caspase-1 immunoreactivity was detected in ganglion cell layer and inner nuclear layer (INL) in vehicle-treated I/R injury group than in AZT-treated I/R injury group. Conclusion: AZT treatment resulted in relative preservation of retinal structure and function following ischemic insult as compared with controls. This suggests AZT may have therapeutic value in the management of retinal ischemic diseases. FAU - Gange, William S AU - Gange WS AD - Health Sciences Division, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA. FAU - Qiao, James B AU - Qiao JB AD - Health Sciences Division, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA. FAU - Park, Paul J AU - Park PJ AD - Health Sciences Division, Department of Ophthalmology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA. FAU - McDonnell, James F AU - McDonnell JF AD - Health Sciences Division, Department of Ophthalmology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA. FAU - Tan, Zhiqun AU - Tan Z AD - Institute for Neurological Impairments and Neurological Disorders, University of California Irvine, Irvine, California, USA. FAU - Perlman, Jay I AU - Perlman JI AD - Health Sciences Division, Department of Ophthalmology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA. AD - Surgery Service and Edward Hines Jr. VA Hospital, Hines, Illinois, USA. FAU - Bu, Ping AU - Bu P AUID- ORCID: 0000-0003-3526-1326 AD - Health Sciences Division, Department of Ophthalmology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA. AD - Research Service, Edward Hines Jr. VA Hospital, Hines, Illinois, USA. LA - eng PT - Journal Article DEP - 20210826 PL - United States TA - J Ocul Pharmacol Ther JT - Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics JID - 9511091 RN - 0 (Pharmaceutical Vehicles) RN - 0 (Reverse Transcriptase Inhibitors) RN - 4B9XT59T7S (Zidovudine) RN - EC 3.4.22.36 (Casp1 protein, mouse) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Animals MH - Apoptosis MH - Caspase 1/metabolism MH - Disease Models, Animal MH - Electroretinography MH - In Situ Nick-End Labeling MH - Injections, Intraperitoneal MH - Mice MH - Mice, Inbred C57BL MH - Night Vision/physiology MH - Pharmaceutical Vehicles MH - Reperfusion Injury/*drug therapy/physiopathology MH - Retina/*physiology MH - Reverse Transcriptase Inhibitors/*therapeutic use MH - Zidovudine/*therapeutic use OTO - NOTNLM OT - apoptosis OT - caspase-1 OT - electroretinogram OT - ischemia/reperfusion injury OT - nucleoside reverse transcriptase inhibitors OT - retinal ischemia OT - zidovudine EDAT- 2021/08/28 06:00 MHDA- 2022/01/22 06:00 CRDT- 2021/08/27 12:15 PHST- 2021/08/28 06:00 [pubmed] PHST- 2022/01/22 06:00 [medline] PHST- 2021/08/27 12:15 [entrez] AID - 10.1089/jop.2020.0083 [doi] PST - ppublish SO - J Ocul Pharmacol Ther. 2021 Oct;37(8):485-491. doi: 10.1089/jop.2020.0083. Epub 2021 Aug 26.