Dr. Eells is Associate Professor of Pharmacology and Toxicology at the University of Wisconsin-Milwaukee. She is widely recognized as an expert in neurotoxicology and the mechanisms of retinal and optic nerve toxicity, and has served as an advisor and consultant to pharmaceutical companies, government agencies, and the World Health Organization. She has in-depth knowledge of physiology, pharmacology, neurobiology and toxicology with particular expertise in ocular toxicology. Her research focuses on the role of mitochondrial dysfunction and reactive oxygen species in retinal and optic nerve disease processes. Her laboratory has been involved in the development and evaluation of new technologies for the analysis and investigation of ion channel physiology, mitochondrial bioenergetics, retinal cell metabolism and photoreceptor function.
Mitochondrial Dysfunction in the Aging Retina.
Biology (Basel). 2019 May 11;8(2):
Authors: Eells JT
Mitochondria are central in retinal cell function and survival and they perform functions that are critical to cell function. Retinal neurons have high energy requirements, since large amounts of ATP are needed to generate membrane potentials and power membrane pumps. Mitochondria over the course of aging undergo a number of changes. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species (ROS) generation and increased numbers of mtDNA mutations. Mitochondria in the neural retina and the retinal pigment epithelium are particularly susceptible to oxidative damage with aging. Many age-related retinal diseases, including glaucoma and age-related macular degeneration, have been associated with mitochondrial dysfunction. Therefore, mitochondria are a promising therapeutic target for the treatment of retinal disease.
PMID: 31083549 [PubMed]
Photoreceptor Survival Is Regulated by GSTO1-1 in the Degenerating Retina.
Invest Ophthalmol Vis Sci. 2018 Sep 04;59(11):4362-4374
Authors: Fernando N, Wooff Y, Aggio-Bruce R, Chu-Tan JA, Jiao H, Dietrich C, Rutar M, Rooke M, Menon D, Eells JT, Valter K, Board PG, Provis J, Natoli R
Purpose: Glutathione-S-transferase omega 1-1 (GSTO1-1) is a cytosolic glutathione transferase enzyme, involved in glutathionylation, toll-like receptor signaling, and calcium channel regulation. GSTO1-1 dysregulation has been implicated in oxidative stress and inflammation, and contributes to the pathogenesis of several diseases and neurological disorders; however, its role in retinal degenerations is unknown. The aim of this study was to investigate the role of GSTO1-1 in modulating oxidative stress and consequent inflammation in the normal and degenerating retina.
Methods: The role of GSTO1-1 in retinal degenerations was explored by using Gsto1-/- mice in a model of retinal degeneration. The expression and localization of GSTO1-1 were investigated with immunohistochemistry and Western blot. Changes in the expression of inflammatory (Ccl2, Il-1β, and C3) and oxidative stress (Nox1, Sod2, Gpx3, Hmox1, Nrf2, and Nqo1) genes were investigated via quantitative real-time polymerase chain reaction. Retinal function in Gsto1-/- mice was investigated by using electroretinography.
Results: GSTO1-1 was localized to the inner segment of cone photoreceptors in the retina. Gsto1-/- photo-oxidative damage (PD) mice had decreased photoreceptor cell death as well as decreased expression of inflammatory (Ccl2, Il-1β, and C3) markers and oxidative stress marker Nqo1. Further, retinal function in the Gsto1-/- PD mice was increased as compared to wild-type PD mice.
Conclusions: These results indicate that GSTO1-1 is required for inflammatory-mediated photoreceptor death in retinal degenerations. Targeting GSTO1-1 may be a useful strategy to reduce oxidative stress and inflammation and ameliorate photoreceptor loss, slowing the progression of retinal degenerations.
PMID: 30193308 [PubMed - in process]
Cuban Epidemic Neuropathy: Insights into the Toxic-Nutritional Hypothesis through International Collaboration.
MEDICC Rev. 2018 Apr;20(2):27-31
Authors: González-Quevedo A, Santiesteban-Freixas R, Eells JT, Lima L, Sadun AA
From 1991 to 1993, an epidemic of optic and peripheral neuropathy-the largest of the century-broke out in Cuba, affecting more than 50,000 people. Initially the main clinical features were decreased visual acuity, central and cecocentral scotomas, impaired color vision and absence of the papillomacular bundle. Later, peripheral and mixed optic-peripheral forms began to appear. Due to the magnitude of the epidemic, the Cuban government requested help from the international community at the 46th World Health Assembly in 1993. PAHO and WHO immediately responded by sending a mission of international experts. Several hypotheses regarding the pathogenesis of Cuban epidemic neuropathy were put forward including: toxic, nutritional, genetic and infectious. The authors refer to extensive studies by researchers sponsored by the Cuban government and PAHO/WHO, joined by scientists from several other countries, including the USA. This paper describes their multidisciplinary work, particularly devoted to investigating the hypothesis of a primary toxic-nutritional cause of the epidemic. Clinical aspects, such as case definition and clinical description, were vital issues from the start. Cuban physicians who first examined patients received a clear impression of its toxic-nutritional origin, later confirmed by international experts. Research then focused on the mechanisms contributing to damage under the toxic-nutritional hypothesis. These included injuries to the mitochondrial oxidative phosphorylation pathway, nutritional deficiencies, excitotoxicity, formate toxicity and dysfunction of the blood-brain barrier. It was expected that the results of such international collaboration into this major health problem would also shed more light on mechanisms underlying other nutritional or tropical myeloneuropathies. KEYWORDS Optic neuritis, optic neuropathy, peripheral neuropathy, neurotoxicity syndromes, disease outbreaks, international cooperation, Cuba Erratum: Page 30, first complete paragraph, line 7, "Two models were developed independently by Cuban researchers" should read "Two models were developed independently by AAS and AGQ."
PMID: 29773773 [PubMed - in process]
Understanding the antimicrobial activity of selected disinfectants against methicillin-resistant Staphylococcus aureus (MRSA).
PLoS One. 2017;12(10):e0186375
Authors: Aboualizadeh E, Bumah VV, Masson-Meyers DS, Eells JT, Hirschmugl CJ, Enwemeka CS
Disinfectants and biocidal products have been widely used to combat Methicillin-resistant Staphylococcus aureus (MRSA) infections in homes and healthcare environments. Although disruption of cytoplasmic membrane integrity has been documented as the main bactericidal effect of biocides, little is known about the biochemical alterations induced by these chemical agents. In this study, we used Fourier transform infrared (FT-IR) spectroscopy and chemometric tools as an alternative non-destructive technique to determine the bactericidal effects of commonly used disinfectants against MRSA USA-300. FTIR spectroscopy permits a detailed characterization of bacterial reactivity, allowing an understanding of the fundamental mechanism of action involved in the interaction between bacteria and disinfectants. The disinfectants studied were ethanol 70% (N = 5), isopropanol (N = 5), sodium hypochlorite (N = 5), triclosan (N = 5) and triclocarban (N = 5). Results showed less than 5% colony forming units growth of MRSA treated with triclocarban and no growth in the other groups. Nearly 70,000 mid-infrared spectra from the five treatments and the two control (untreated; N = 4) groups of MRSA (bacteria grown in TSB and incubated at 37°C (Control I) / at ambient temperature (Control II), for 24h) were pre-processed and analyzed using principal component analysis followed by linear discriminant analysis (PCA-LDA). Clustering of strains of MRSA belonging to five treatments and the discrimination between each treatment and two control groups in MRSA (untreated) were investigated. PCA-LDA discriminatory frequencies suggested that ethanol-treated spectra are the most similar to isopropanol-treated spectra biochemically. Also reported here are the biochemical alterations in the structure of proteins, lipid membranes, and phosphate groups of MRSA produced by sodium hypochlorite, triclosan, and triclocarban treatments. These findings provide mechanistic information involved in the interaction between MRSA strains and hygiene products; thereby demonstrating the potential of spectroscopic analysis as an objective, robust, and label-free tool for evaluating the macromolecular changes involved in disinfectant-treated MRSA.
PMID: 29036196 [PubMed - indexed for MEDLINE]
Low-intensity far-red light inhibits early lesions that contribute to diabetic retinopathy: in vivo and in vitro.
Invest Ophthalmol Vis Sci. 2013 May;54(5):3681-90
Authors: Tang J, Du Y, Lee CA, Talahalli R, Eells JT, Kern TS
PURPOSE: Treatment with light in the far-red to near-infrared region of the spectrum (photobiomodulation [PBM]) has beneficial effects in tissue injury. We investigated the therapeutic efficacy of 670-nm PBM in rodent and cultured cell models of diabetic retinopathy.
METHODS: Studies were conducted in streptozotocin-induced diabetic rats and in cultured retinal cells. Diabetes-induced retinal abnormalities were assessed functionally, biochemically, and histologically in vivo and in vitro.
RESULTS: We observed beneficial effects of PBM on the neural and vascular elements of retina. Daily 670-nm PBM treatment (6 J/cm(2)) resulted in significant inhibition in the diabetes-induced death of retinal ganglion cells, as well as a 50% improvement of the ERG amplitude (photopic b wave responses) (both P < 0.01). To explore the mechanism for these beneficial effects, we examined physiologic and molecular changes related to cell survival, oxidative stress, and inflammation. PBM did not alter cytochrome oxidase activity in the retina or in cultured retinal cells. PBM inhibited diabetes-induced superoxide production and preserved MnSOD expression in vivo. Diabetes significantly increased both leukostasis and expression of ICAM-1, and PBM essentially prevented both of these abnormalities. In cultured retinal cells, 30-mM glucose exposure increased superoxide production, inflammatory biomarker expression, and cell death. PBM inhibited all of these abnormalities.
CONCLUSIONS: PBM ameliorated lesions of diabetic retinopathy in vivo and reduced oxidative stress and cell death in vitro. PBM has been documented to have minimal risk. PBM is noninvasive, inexpensive, and easy to administer. We conclude that PBM is a simple adjunct therapy to attenuate the development of diabetic retinopathy.
PMID: 23557732 [PubMed - indexed for MEDLINE]
Photobiomodulation induced by 670 nm light ameliorates MOG35-55 induced EAE in female C57BL/6 mice: a role for remediation of nitrosative stress.
PLoS One. 2013;8(6):e67358
Authors: Muili KA, Gopalakrishnan S, Eells JT, Lyons JA
BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is the most commonly studied animal model of multiple sclerosis (MS), a chronic autoimmune demyelinating disorder of the central nervous system. Immunomodulatory and immunosuppressive therapies currently approved for the treatment of MS slow disease progression, but do not prevent it. A growing body of evidence suggests additional mechanisms contribute to disease progression. We previously demonstrated the amelioration of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in C57BL/6 mice by 670 nm light-induced photobiomodulation, mediated in part by immune modulation. Numerous other studies demonstrate that near-infrared/far red light is therapeutically active through modulation of nitrosoxidative stress. As nitric oxide has been reported to play diverse roles in EAE/MS, and recent studies suggest that axonal loss and progression of disability in MS is mediated by nitrosoxidative stress, we investigated the effect of 670 nm light treatment on nitrosative stress in MOG-induced EAE.
METHODOLOGY: Cell culture experiments demonstrated that 670 nm light-mediated photobiomodulation attenuated antigen-specific nitric oxide production by heterogenous lymphocyte populations isolated from MOG immunized mice. Experiments in the EAE model demonstrated down-regulation of inducible nitric oxide synthase (iNOS) gene expression in the spinal cords of mice with EAE over the course of disease, compared to sham treated animals. Animals receiving 670 nm light treatment also exhibited up-regulation of the Bcl-2 anti-apoptosis gene, an increased Bcl-2:Bax ratio, and reduced apoptosis within the spinal cord of animals over the course of disease. 670 nm light therapy failed to ameliorate MOG-induced EAE in mice deficient in iNOS, confirming a role for remediation of nitrosative stress in the amelioration of MOG-induced EAE by 670 nm mediated photobiomodulation.
CONCLUSIONS: These data indicate that 670 nm light therapy protects against nitrosative stress and apoptosis within the central nervous system, contributing to the clinical effect of 670 nm light therapy previously noted in the EAE model.
PMID: 23840675 [PubMed - indexed for MEDLINE]
Inhibitory effects of 405 nm irradiation on Chlamydia trachomatis growth and characterization of the ensuing inflammatory response in HeLa cells.
BMC Microbiol. 2012;12:176
Authors: Wasson CJ, Zourelias JL, Aardsma NA, Eells JT, Ganger MT, Schober JM, Skwor TA
BACKGROUND: Chlamydia trachomatis is an intracellular bacterium that resides in the conjunctival and reproductive tract mucosae and is responsible for an array of acute and chronic diseases. A percentage of these infections persist even after use of antibiotics, suggesting the need for alternative treatments. Previous studies have demonstrated anti-bacterial effects using different wavelengths of visible light at varying energy densities, though only against extracellular bacteria. We investigated the effects of visible light (405 and 670 nm) irradiation via light emitting diode (LEDs) on chlamydial growth in endocervical epithelial cells, HeLa, during active and penicillin-induced persistent infections. Furthermore, we analyzed the effect of this photo treatment on the ensuing secretion of IL-6 and CCL2, two pro-inflammatory cytokines that have previously been identified as immunopathologic components associated with trichiasis in vivo.
RESULTS: C. trachomatis-infected HeLa cells were treated with 405 or 670 nm irradiation at varying energy densities (0 - 20 J/cm2). Bacterial growth was assessed by quantitative real-time PCR analyzing the 16S: GAPDH ratio, while cell-free supernatants were examined for IL-6 and monocyte chemoattractant protein-1 (CCL2) production. Our results demonstrated a significant dose-dependent inhibitory effect on chlamydial growth during both active and persistent infections following 405 nm irradiation. Diminished bacterial load corresponded to lower IL-6 concentrations, but was not related to CCL2 levels. In vitro modeling of a persistent C. trachomatis infection induced by penicillin demonstrated significantly elevated IL-6 levels compared to C. trachomatis infection alone, though 405 nm irradiation had a minimal effect on this production.
CONCLUSION: Together these results identify novel inhibitory effects of 405 nm violet light on the bacterial growth of intracellular bacterium C. trachomatis in vitro, which also coincides with diminished levels of the pro-inflammatory cytokine IL-6.
PMID: 22894815 [PubMed - indexed for MEDLINE]
Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light.
PLoS One. 2012;7(1):e30655
Authors: Muili KA, Gopalakrishnan S, Meyer SL, Eells JT, Lyons JA
BACKGROUND: The approved immunomodulatory agents for the treatment of multiple sclerosis (MS) are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE) model of multiple sclerosis.
METHODOLOGY/PRINCIPAL FINDINGS: The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG) according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham) administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α) and up-regulation of anti-inflammatory cytokines (IL-4, IL-10) in vitro and in vivo.
CONCLUSION/SIGNIFICANCE: These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response.
PMID: 22292010 [PubMed - indexed for MEDLINE]
Therapeutic effect of near infrared (NIR) light on Parkinson's disease models.
Front Biosci (Elite Ed). 2012;4:818-23
Authors: Quirk BJ, Desmet KD, Henry M, Buchmann E, Wong-Riley M, Eells JT, Whelan HT
Parkinson's disease (PD) is a neurodegenerative disorder that affects large numbers of people, particularly those of a more advanced age. Mitochondrial dysfunction plays a central role in PD, especially in the electron transport chain. This mitochondrial role allows the use of inhibitors of complex I and IV in PD models, and enhancers of complex IV activity, such as NIR light, to be used as possible therapy. PD models fall into two main categories; cell cultures and animal models. In cell cultures, primary neurons, mutant neuroblastoma cells, and cell cybrids have been studied in conjunction with NIR light. Primary neurons show protection or recovery of function and morphology by NIR light after toxic insult. Neuroblastoma cells, with a gene for mutant alpha-synuclein, show similar results. Cell cybrids, containing mtDNA from PD patients, show restoration of mitochondrial transport and complex I and IV assembly. Animal models include toxin-insulted mice, and alpha-synuclein transgenic mice. Functional recovery of the animals, chemical and histological evidence, and delayed disease progression show the potential of NIR light in treating Parkinson's disease.
PMID: 22201916 [PubMed - indexed for MEDLINE]
Effects of low-level light therapy on streptozotocin-induced diabetic kidney.
J Photochem Photobiol B. 2010 May 3;99(2):105-10
Authors: Lim J, Sanders RA, Snyder AC, Eells JT, Henshel DS, Watkins JB
Hyperglycemia causes oxidative damage in tissues prone to complications in diabetes. Low-level light therapy (LLLT) in the red to near infrared range (630-1000nm) has been shown to accelerate diabetic wound healing. To test the hypothesis that LLLT would attenuate oxidative renal damage in Type I diabetic rats, male Wistar rats were made diabetic with streptozotocin (50mg/kg, ip), and then exposed to 670nm light at a dose of 9J/cm(2) once per day for 14weeks. The activity and expression of catalase and the activity of Na K-ATPase increased in kidneys of light-treated diabetic rats, whereas the activity and expression of glutathione peroxidase and the expression of Na K-ATPase were unchanged. LLLT lowered the values of serum BUN, serum creatinine, and BUN/creatinine ratio. In addition, LLLT augmented the activity and expression of cytochrome c oxidase, a primary photoacceptor molecule in the mitochondrial respiratory chain, and reduced the formation of the DNA adduct 8-hydroxy-2'-deoxyguanosine in kidney. LLLT improved renal function and antioxidant defense capabilities in the kidney of Type I diabetic rats. Thus, 670nm LLLT may be broadly applicable to the amelioration of renal complications induced by diabetes that disrupt antioxidant defense mechanisms.
PMID: 20356759 [PubMed - indexed for MEDLINE]