Tom Johnson's Schools

• Johns Hopkins University , Class of 2014 MD in Medicine

• University of Cambridge , Class of 2010 Ph.D in Neuroscience

• Northwestern University , Class of 2005 Bachelors in Biology and Chemistry

Tom Johnson's Affiliations

• Gates Cambridge Scholars 2006

• Association for Research in Vision and Ophthalmology (ARVO) 2005 ARVO is the largest and most respected eye and vision research organization in the world. Our members include more than 12,000 researchers from 73 countries. ARVO encourages and assists research, training, publication and knowledge-sharing in vision and ophthalmology.

• Delta Chi Northwestern University 2002 - 2005

• Phi Beta Kappa Northwestern University 2005

• Alpha Lambda Delta Northwestern University 2003

Tom Johnson's Publications

• Bacterial DNA confers neuroprotection after optic nerve injury by suppressing CD4+CD25+ regulatory T-cell activity., Investigative Ophthalmology and Visual Science August, 2007 PURPOSE: Protective autoimmunity attenuates secondary degeneration after central nervous system (CNS) injury. Such neuroprotection is achieved via activation of autoimmune CD4CD25 effector T cells (Teffs) or suppression of naturally occurring CD4CD25 regulatory T cells (Tregs). In this study the ability of bacterial DNA, characterized by unmethylated CpG islands, to downregulate Treg activity and therefore, to confer neuroprotection was investigated. METHODS: The effects of CpG on suppressive activity of mouse Tregs were studied by coculturing Tregs with Teffs and measuring proliferation by radiolabeled thymidine. The neuroprotective effects of CpG-mediated Treg suppression was examined in rats after optic nerve crush. RESULTS: Teff proliferation in response to T-cell receptor stimuli was significantly reduced when the Teffs were cocultured with Tregs, compared with Teff activation when cultured alone. Treating Tregs with CpG reduced their suppressive activity and restored Teff proliferation to baseline levels. CpG injection in rats with optic nerve crush conferred significant neuroprotection compared with that in untreated control rats (118 +or 8 cells/mm(2) vs. 69 +or- 5 cells/mm(2), respectively; mean +or- SEM; P < 0.05). CpG-mediated neuroprotection was accompanied by significantly increased T-cell infiltration at the injury site. Similar CpG treatment of athymic nude rats yielded no neuroprotection, further suggesting a T-cell-dependent mechanism of CpG action. CONCLUSIONS: These findings strongly support the notion that alleviation of Treg suppression after injury benefits neuronal survival. Bacterial DNA attenuation of Treg suppressive activity may represent an evolutionary adaptation that curbs the amplified infection risk after CNS trauma, due to blood-brain barrier breakdown. This study may prompt development of new neuroprotective therapies aimed at the immune system, to benefit the injured CNS.

• T cell independent mechanism for copolymer-1-induced neuroprotection., European Journal of Immunology November, 2007 Despite active investigation of copolymer-1 (Cop-1) for nearly 40 years the mechanisms underlying its neuroprotective properties remain contentious. Nonetheless, current dogma for Cop-1 neuroprotective activities in autoimmune and neurodegenerative diseases include bystander suppression of autoimmune T cells and attenuation of microglial responses. In this report, we demonstrate that Cop-1 interacts directly with primary human neurons and decreases neuronal cell death induced by staurosporine or oxidative stress. This neuroprotection is mediated through protein kinase Calpha and brain-derived neurotrophic factor. Dendritic cells (DC) uptake Cop-1, deliver it to the injury site, and release it in an active form. Interactions between Cop-1 and DC enhance DC blood brain barrier migration. In a rat model with optic nerve crush injury, Cop-1-primed DC induce T cell independent neuroprotection. These findings may facilitate the development of neuroprotective approaches using DC-mediated Cop-1 delivery to diseased nervous tissue.

• Toll-like receptors: roles in neuroprotection?, Trends in Neurosciences March, 2008 Toll-like receptors (TLRs) enable mammalian cells to sense pathogenic challenges. They are essential for appropriate initiation, execution and regulation of innate and adaptive immune responses. Whereas TLR-mediated processes in the central nervous system (CNS) might contribute to detrimental (auto)immune reactions, they are unlikely to have exclusively neurodestructive consequences. Indeed, appropriately controlled TLR signaling might be crucial for preserving CNS structure and function in certain contexts. Recent findings illustrate neuroprotective capacities for TLRs, mediated by containment of trauma-associated infection or by recruitment of neuroprotective T lymphocytes. By the latter mechanism, endogenous or therapeutically administered TLR ligands could conceivably generate neuroprotective benefits in noninfectious CNS disorders. This article focuses on the yet less-addressed protective potential of TLR engagement within the CNS.

• Effects of central corneal thickness on the efficacy of topical ocular hypotensive medications., Journal of Glaucoma March, 2008 PURPOSE: To determine the effect of central corneal thickness (CCT) on the efficacy of intraocular pressure (IOP)-reducing drugs in patients with ocular hypertension (OHT). METHODS: This retrospective study analyzed research records of 115 OHT patients and 97 ocular normotensive (ONT) volunteers. CCT was measured by slit-lamp pachymetry and IOP by pneumatonometry. The OHT patients were divided into Thick (greater than 540 microm, n=52) and Thin (less than or equal to 540 microm, n=63) Cornea groups. Measurements in the OHT group were made after washout of all IOP-lowering drugs and at 1 week of treatment with latanoprost 0.005%, dorzolamide 2%, brimonidine 0.2%, apraclonidine 0.5%, pilocarpine 2%, or unoprostone 0.15% to 1 eye and vehicle contralaterally. ONT volunteers also were divided into Thick (n=34) and Thin (n=63) Cornea groups. Results were compared between groups using unpaired t tests or nonparametric Wilcoxon tests and within groups using linear regression analyses. RESULTS: Baseline IOPs were not different between CCT groups of OHT patients or of ONT volunteers. After 1 week of drug treatment, IOP was significantly (P=0.02) lower in the OHT Thin Cornea group (16.0+/-3.0 mm Hg, mean+/-SD) than the OHT Thick Cornea group (17.4+/-2.8 mm Hg). There was a positive correlation between IOP and CCT (R=0.06, P=0.007) in OHT drug-treated eyes, but not OHT vehicle-treated or ONT untreated eyes. The final IOP was significantly lower in the Thin than the Thick Cornea group treated with brimonidine (P=0.02) but not with latanoprost (P=0.91). CONCLUSIONS: When dosed with IOP lowering drugs, eyes with thinner corneas had lower IOPs than eyes with thicker corneas. This suggests a reduced efficacy of some glaucoma medications in ocular hypertensive patients with thick corneas.

• Rebound tonometry in conscious, conditioned mice avoids the acute and profound effects of anesthesia on intraocular pressure., Journal of Ocular Pharmacology and Therapeutics April, 2008 AIMS: The aims of this study were to evaluate the accuracy, repeatability, and safety of multiple intraocular pressure (IOP) measurements by a commercially available rebound tonometer in conscious, conditioned mice, and to characterize the acute and profound effects of anesthesia on IOP in mice. METHODS: To test the accuracy of the tonometer, IOPs of CD-1 mice under ketamine/xylazine anesthesia were experimentally set and monitored with a water manometer/transducer system following transcorneal cannulation while simultaneously performing tonometry. The long- and short-term repeatability of the tonometer was tested in conscious, restrained mice, as measurements were taken once-daily in the afternoon for 4 consecutive days. On day 5, IOPs were measured in the same mice once every 4 min for 32 min. On 2 separate days, mice were administered ketamine/xylazine or 2,2,2-tribromoethanol anesthesia, in a crossover design, and IOPs were measured once every 2 min for 32 min. Rebound tonometry was performed in conscious mice before and 1 hour after 1 drop of timolol maleate (10 microL of 0.5%) application to 1 eye. RESULTS: IOP measurements by rebound tonometry correlated well with manometry for pressures between 8 and 38 mmHg (y = 0.98x – 0.32, R(2) = 0.94; P < 0.001). The average tonometric IOP was invariant over 4 days (range, 11.7-13.2 mmHg). IOPs dropped significantly ( P < or = 0.05) within 6 min (ketamine/xylazine) or 10 min (2,2,2-tribromoethanol) postadministration of anesthesia but not with conscious restraint. Timolol significantly (P < 0.001) lowered IOP from 12.8 +or- 0.3 (mean +or- standard error of the mean) to 10.1 +or- 0.6 mmHg, as measured by the tonometer. CONCLUSIONS: Rebound tonometry can be used to obtain accurate IOP measurements in conscious, restrained mice while avoiding the rapid and profound ocular hypotensive effects of general anesthesia. Small changes in IOP with an aqueous-flow suppressant are readily detectable with conscious restraint that may be missed with chemical restraint.

• Development and characterization of an adult retinal explant organotypic tissue culture system as an in vitro intraocular stem cell transplantation model., Investigative Ophthalmology and Visual Science June, 2008 Purpose: To develop and characterize a retinal explant culture system to facilitate investigation of novel methods of improving retinal stem cell therapy. Methods: Retinas explanted from adult rats were cultured in serum-free media (B27/N2) or media containing normal horse serum (NHS). Tissue viability was assessed by gross morphology, propidium iodide (PI) uptake, cell survival quantification, activated caspase-3 expression, and immunohistochemistry. To model intravitreal cell transplantation, Muller progenitor cells (hMIO-M1) or mesenchymal stem cells (MSC) were placed on explants. Explants were compared to whole eyes with or without experimental glaucoma and/or intravitreal cell transplantation. Results: Explants cultured in B27/N2 media were viable for at least 17 days as assessed by the aforementioned parameters. NHS media was associated with obvious tissue degradation; greater/more diffuse PI uptake; significant cell loss over time; and temporal increase in activated caspase-3(+) cells. Explants in B27/N2 media strongly expressed beta-III-tubulin, neurofilament, NeuN, Brn3a, Thy-1, GFAP, vimentin, nestin, and glutamine synthetase, whereas immunoreactivity was weak in NHS media and decreased further with time. Seven and fourteen days after co-culture or transplantation, glial reactivity (GFAP/vimentin expression) was highly upregulated in explants and eyes, respectively. Some grafted cells migrated into the retina, but the majority remained outside the inner limiting membrane. Conclusions: Retinal explants prepared using our techniques and cultured in B27/N2 media are viable for at least 2 weeks and mimic in vivo glial reactivity to transplantation while allowing few grafted cells to integrate. This system may be a useful in vitro model for investigating methods to enhance retinal stem cell therapy.

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