Macrophage Migration Inhibitor (MIF) Therapeutics for Neuroprotection and Prevention of Scar in Traumatic Retinal Detachment
Abstract
Retinal detachment (RD) is a prevalent cause of blindness that is common after ocular injury to military personnel. Permanent vision loss occurs due to death of photoreceptors and formation of excessive scar tissue, known as proliferative vitreoretinopathy (PVR). There are no effective pharmaceuticals to prevent these problems. The inflammatory protein, macrophage migration inhibitory factor (MIF), is produced at high levels in RD and PVR, as well as in excitotoxic (NMDA-mediated) damage, which is important in blast injury. We tested the ability of different clinically-relevant MIF inhibitors to block photoreceptor death after NMDA damage in a chick excitotoxic retinal damage model. These inhibitors, ibudilast, AV1013, and CPSI-1306, are well tolerated in the eye, and treatment with the maximum dose of each drug does not show retinal toxicity. Ibudilast pretreatment significantly reduced the number of TUNEL positive cells in the retina after NMDA damage. CPSI-1306 also reduced TUNEL. AV1013 had no effect. Ibudilast and AV1013 also blocked epithelial mesenchymal transition in the invitro PVR model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1125479
Entities
People
- Abhay R Satoskar
- Andrew J. Fischer
- Bayan Shalash
- Colleen Cebulla
- Elizabeth Urbanski
- Hailey Wilson
- Julie Racine
- Krupa Patel
- Mohamed Soumakieh
- Mohd H. Shah
- Richard Wan
- Sumaya Hamadmad
- Tyler Heisler-Taylor
- Yushin Jeng
Organizations
- Ohio State University