Neurotrauma
Every year in the U.S, approximately 3 million people incur a traumatic brain injury (TBI). Nearly 80% of these individuals self-report visual dysfunction. In addition, 2-5% lose vision permanently as a result of indirect trauma to their optic nerve, i.e. ITON. We have both clinical and laboratory-based research on this population. In our clinical study we are collaborating with many colleagues to identify a diagnostic battery for audiological and visual dysfunction after a TBI. Diagnostics are key for determining safe return to duty/work/play. They are also important for the development and testing of interventions.
In our laboratory studies we use animal models of ITON to investigate mechanisms and determine the efficacy of rational therapies for mitigation of vision loss after trauma. We are investigating both neuroprotective and neuroregenerative approaches. We have found that our model of trauma causes elevated reactive oxygen species, which leads to an increase in IL-1 and activation of the inflammasome. Inhibiting these pathways protects the optic nerve and vision
Glaucoma Neuroprotection
A more common optic nerve degeneration is glaucoma. Glaucoma is a leading cause of blindness world-wide. There is no clear genetic cause for most forms of glaucoma and lowering IOP is not entirely effective for many patients. We are interested in IOP-independent neuroprotective strategies to preserve vision. We have patents on a form of erythropoietin that has attenuated erythropoietic activity, but full neuroprotective activity (EPO-R76E). We have shown that it is protective in multiple models of glaucoma and optic nerve injury. We are now actively investigating its mechanism of action with the goal of also gaining insight into glaucoma pathogenesis. We have shown that EPO-R76E activates expression of antioxidant proteins. We are exploring the role of this antioxidant pathway in a cell-type specific manner in an inducible model of glaucoma.
Recent Publications
Bernardo-Colón A, Vest V, Clark AF, Cooper M, Calkins DJ, Harrison FE, Rex TS. (2018) Antioxidants prevent inflammation and preserve the optic projection and visual function in experimental neurotrauma. Cell Death & Dis. 9:1097.
Vest V, Bernardo-Colón A, Watkins, D, Kim B, Rex TS. (2019) Rapid repeat exposure to sub-threshold trauma causes synergistic axonal damage and functional deficits in the visual pathway in a mouse model. J. Neurotrauma. 36:1646-1654.
Bernardo-Colón A, Vest V, Cooper M, Calkins DJ, Rex TS. (2019) Progression and pathology of blast-induced indirect traumatic optic neuropathy. Frontiers Neurosci. 13:719.
Naguib S, Bernardo-Colón A, Cencer C, Gandra N, Rex TS. (2019) Galantamine protects against synaptic, axonal, and vision deficits in experimental neurotrauma. Neurobiology of Disease 25:104695
Backstrom JR, Sheng J, Wang MC, Bernardo-Colón A, Rex TS. (2020) Optimization of S. aureus dCas9 and CRISPRi Elements for a Single Adeno-Associated Virus that Targets an Endogenous Gene. Mol Therapy Methods & Clin Develop. 19: 139-148.
DeJulius CR, Bernardo-Colón A, Naguib S, Backstrom JR, Collins T, Gupta M, Duvall C, Rex TS. (2020) Sustained delivery of erythropoietin-R76E via PPS microparticles is more protective than delivery via PLGA particles in a mouse model of indirect traumatic optic neuropathy. J Controlled Release. Epub