CB2 Receptor Therapy Using the FDA-Approved Drug Raloxifene to Mitigate Visual Deficits after Mild TBI and/or Ocular Trauma
Abstract
Visual deficits after traumatic brain injury (TBI) or after non-rupturing ocular trauma are highly common in the military, but interventions that limit the post-trauma visual impairments have not been identified. We have found that treatment with a CB2 cannabinoid receptor inverse agonist for 2 weeks after closed-head blast TBI greatly attenuates the visual deficits and retinal pathology produced by mild traumatic brain injury in mice, apparently by modulating the otherwise deleterious role of microglia in the injury process after trauma. The drug we have used (SMM189), however, has not yet been approved for human use. Raloxifene is an FDA approved estrogen receptor drug that is used to treat osteoporosis, but was recently found to show noteworthy CB2 inverse agonism. In the current studies, we are testing the benefit of raloxifene for reducing visual deficits and retinal and optic nerve damage from mild TBI and closed-globe ocular injury in mice. In the fourth year of the project, we have been determining if raloxifene reduces visual deficits and pathology, when delivered daily after TBI produced using dorsal cranial impact injury or single or repeat ocular blast injury (OBI). Visual system injury and its abatement with raloxifene was assessed by functional testing (visual acuity, contrast sensitivity, the scotopic electroretinogram, pupil light response, and light aversion) and morphological analysis of retina, optic nerve, optic tract, central visual structures and oculomotor nerves. We found that raloxifene for impact TBI and OBI reduces functional deficits, and mitigates the underlying visual system pathology and inflammatory response, seemingly by modulating microglia to a more beneficial state.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2020
- Accession Number
- AD1106946
Entities
People
- Anton Reiner
Organizations
- University of Tennessee