Digital Commons Network^™

Virtual Reality As A Training Tool To Treat Physical Inactivity In Children, Adam W. Kiefer, David Pincus, Michael J. Richardson, Gregory D. Myer

Psychology Faculty Articles and Research

Lack of adequate physical activity in children is an epidemic that can result in obesity and other poor health outcomes across the lifespan. Physical activity interventions focused on motor skill competence continue to be developed, but some interventions, such as neuromuscular training (NMT), may be limited in how early they can be implemented due to dependence on the child’s level of cognitive and perceptual-motor development. Early implementation of motor-rich activities that support motor skill development in children is critical for the development of healthy levels of physical activity that carry through into adulthood. Virtual reality (VR) training may be beneficial …

Ran Translation At C9orf72-Associated Repeat Expansions Is Selectively Enhanced By The Integrated Stress Response, Katelyn M. Green, M. Rebecca Glineburg, Michael G. Kearse, Brittany N. Flores, Alexander E. Linsalata, Stephen J. Fedak, Aaron C. Goldstrohm, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG (RAN) translation allows for unconventional initiation at disease-causing repeat expansions. As RAN translation contributes to pathogenesis in multiple neurodegenerative disorders, determining its mechanistic underpinnings may inform therapeutic development. Here we analyze RAN translation at G₄C₂ repeat expansions that cause C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause fragile X-associated tremor/ataxia syndrome. We find that C9RAN translation initiates through a cap- and eIF4A-dependent mechanism that utilizes a CUG start codon. C9RAN and CGG RAN are both selectively enhanced by integrated stress response (ISR) activation. ISR-enhanced RAN translation requires an …

Changes In The Utilization Of Osteoporosis Drugs After The 2010 Fda Bisphosphonate Drug Safety Communication, Bander Balkhi, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

Introduction

In October 2010, the US Food and Drug Administration (FDA) issued a safety communication regarding the risks of atypical fractures of the femur, with bisphosphonates drugs. This study evaluated the impact of the bisphosphonates FDA safety communication on the utilization of osteoporosis medications in Medicaid programs.

Methods

Osteoporosis drugs utilization data from the July 2006 to June 2014 were extracted from the national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services (CMS). We performed an interrupted time series analyses to evaluate trends in utilization of osteoporosis drugs before and …

Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and …

The Climate Of Neurofeedback: Scientific Rigour And The Perils Of Ideology, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

Over the last six decades, an in-group with ideological and financial stakes has been conducting sub-par research to develop an ostensibly effective clinical intervention: EEG-neurofeedback. More recently, however, a string of independent studies featuring increased scientific rigour and tighter experimental controls has challenged the foundation on which EEG-neurofeedback stands. Earlier this year, Brain published one of the most robust EEG-neurofeedback experiments to date (Schabus et al., 2017), which sparked a flurry of correspondence concerning the therapeutic value of neurofeedback (Fovet et al., 2017; Schabus, 2017); notably, a parallel discussion continues in Lancet Psychiatry …

Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, Stephanie A. Stout, Jue Lin, Natalie Hernandez, Elyssia Poggi Davis, Judith E. Carroll, Laura M. Glynn

Psychology Faculty Articles and Research

Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva.

Methods: TL …

Combinational Sirna Delivery Using Hyaluronic Acid Modified Amphiphilic Polyplexes Against Cell Cycle And Phosphatase Proteins To Inhibit Growth And Migration Of Triple-Negative Breast Cancer Cells, Manoj B. Parmar, Daniel Nisakar Meenakshi Sundaram, Remant Bahadur Kc, Robert Maranchuk, Hamidreza Montazeri Aliabadi, Judith C. Hugh, Raimar Löbenberg, Hasan Uludağ

Pharmacy Faculty Articles and Research

Triple-negative breast cancer is an aggressive form of breast cancer with few therapeutic options if it recurs after adjuvant chemotherapy. RNA interference could be an alternative therapy for metastatic breast cancer, where small interfering RNA (siRNA) can silence the expression of aberrant genes critical for growth and migration of malignant cells. Here, we formulated a siRNA delivery system using lipid-substituted polyethylenimine (PEI) and hyaluronic acid (HA), and characterized the size, ζ-potential and cellular uptake of the nanoparticulate delivery system. Higher cellular uptake of siRNA by the tailored PEI/HA formulation suggested better interaction of complexes with breast cancer cells due to …

Cortical Contribution To Linear, Non-Linear And Frequency Components Of Motor Variability Control During Standing, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Motor variability is an inherent feature of all human movements and reflects the quality of functional task performance. Depending on the requirements of the motor task, the human sensory-motor system is thought to be able to flexibly govern the appropriate level of variability. However, it remains unclear which neurophysiological structures are responsible for the control of motor variability. In this study, we tested the contribution of cortical cognitive resources on the control of motor variability (in this case postural sway) using a dual-task paradigm and furthermore observed potential changes in control strategy by evaluating Ia-afferent integration (H-reflex). Twenty healthy subjects …

Volition And Action In The Human Brain: Processes, Pathologies, And Reasons, Itzhak Fried, Patrick Haggard, Biyu J. He, Aaron Schurger

Psychology Faculty Articles and Research

Humans seem to decide for themselves what to do, and when to do it. This distinctive capacity may emerge from an ability, shared with other animals, to make decisions for action that are related to future goals, or at least free from the constraints of immediate environmental inputs. Studying such volitional acts proves a major challenge for neuroscience. This review highlights key mechanisms in the generation of voluntary, as opposed to stimulus-driven actions, and highlights three issues. The first part focuses on the apparent spontaneity of voluntary action. The second part focuses on one of the most distinctive, but elusive, …

Theta-Burst Microstimulation In The Human Entorhinal Area Improves Memory Specificity, Ali S. Titiz, Michael R. H. Hill, Emily A. Mankin, Zahra M. Aghajan, Dawn Eliashiv, Natalia Tchemodanov, Uri Maoz, John Stern, Michelle E. Tran, Peter Schuette, Eric Behnke, Nanthia A. Suthana, Itzhak Fried

Psychology Faculty Articles and Research

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm-diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants …

Difatty Acyl-Conjugated Linear And Cyclic Peptides For Sirna Delivery, Hung Do, Meenakshi Sharma, Naglaa Salem El-Sayed, Parvin Mahdipoor, Emira Bousoik, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic difatty acyl linear and cyclic R5K2 peptide conjugates were synthesized by solid-phase peptide methods to enhance the interaction with the hydrophobic cellular phospholipid bilayer and to improve siRNA delivery and silencing. Binding to siRNA molecules was significantly less for the cyclic peptide conjugates. A gradual decrease was observed in the particle size of the complexes with increasing peptide/siRNA ratio for most of the synthesized peptides, suggesting the complex formation. Most of the complexes showed a particle size of less than 200 nm, which is considered an appropriate size for in vitro siRNA delivery. A number of …

Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas

Pharmacy Faculty Articles and Research

Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.

Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …

The Psychology Of Neurofeedback: Clinical Intervention Even If Applied Placebo, Robert T. Thibault, Amir Raz

Psychology Faculty Articles and Research

Advocates of neurofeedback make bold claims concerning brain regulation, treatment of disorders, and mental health. Decades of research and thousands of peer-reviewed publications support neurofeedback using electroencephalography (EEG-nf); yet, few experiments isolate the act of receiving feedback from a specific brain signal as a necessary precursor to obtain the purported benefits. Moreover, while psychosocial parameters including participant motivation and expectation, rather than neurobiological substrates, seem to fuel clinical improvement across a wide range of disorders, for-profit clinics continue to sprout across North America and Europe. Here, we highlight the tenuous evidence supporting EEG-nf and sketch out the weaknesses of this …

Precursor Processes Of Human Self-Initiated Action, Nima Khalighinejad, Aaron Schurger, Andrea Desantis, Leor Zmigrod

Psychology Faculty Articles and Research

A gradual buildup of electrical potential over motor areas precedes self-initiated movements. Recently, such “readiness potentials” (RPs) were attributed to stochastic fluctuations in neural activity. We developed a new experimental paradigm that operationalized self-initiated actions as endogenous ‘skip’ responses while waiting for target stimuli in a perceptual decision task. We compared these to a block of trials where participants could not choose when to skip, but were instead instructed to skip. Frequency and timing of motor action were therefore balanced across blocks, so that conditions differed only in how the timing of skip decisions was generated. We reasoned that across-trial …

A Validated Measure For Fertility Awareness: An Essential Step Toward Informed Reproductive Decision-Making, Brennan Peterson

Marriage and Family Therapy Faculty Articles and Research

"The efforts by Kudesia and colleagues (1) to create and validate a fertility awareness survey is a vital development in the field of reproductive health care. The 29-item Fertility and Infertility Treatment Knowledge Score (FIT-KS) was created to measure fertility awareness and infertility treatment knowledge in the general population and among medical trainees. Using a combination of existing questionnaires, consultation with specialists in test construction, and clinical recommendations of an expert panel of 15 reproductive endocrinologists, the FIT-KS is the first of its kind in the United States. The authors should be commended for their foresight and attempts to address …

Trkb-Enhancer Facilitates Functional Recovery After Traumatic Brain Injury, John Marshall, Joanna Szmydynger-Chodobska, Mengia S. Rioult-Pedotti, Kara Lau, Andrea T. Chin, Siva K. Reddy Kotla, Rakesh Tiwari, Keykavous Parang, Steven W. Threlkeld, Adam Chodobski

Pharmacy Faculty Articles and Research

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the …

Lower Extremity Motor Impairments In Ambulatory Chronic Hemiparetic Stroke: Evidence For Lower Extremity Weakness And Abnormal Muscle And Joint Torque Coupling Patterns, Natalia Sánchez, Ana Maria Acosta, Roberto Lopez-Rosado, Arno H. A. Stienen, Julius P. A. Dewald

Physical Therapy Faculty Articles and Research

Although global movement abnormalities in the lower extremity poststroke have been studied, the expression of specific motor impairments such as weakness and abnormal muscle and joint torque coupling patterns have received less attention. We characterized changes in strength, muscle coactivation and associated joint torque couples in the paretic and nonparetic extremity of 15 participants with chronic poststroke hemiparesis (age 59.6 ± 15.2 years) compared with 8 age-matched controls. Participants performed isometric maximum torques in hip abduction, adduction, flexion and extension, knee flexion and extension, ankle dorsi- and plantarflexion and submaximal torques in hip extension and ankle plantarflexion. Surface electromyograms (EMGs) …

Traceable Peo-Poly(Ester) Micelles For Breast Cancer Targeting: The Effect Of Core Structure And Targeting Peptide On Micellar Tumor Accumulation, Shyam M. Garg, Igor M. Paiva, Mohammad R. Vakili, Rania Soudy, Kate Agopsowicz, Amir H. Soleimani, Mary Hitt, Kamaljit Kaur, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Traceable poly(ethylene oxide)-poly(ester) micelles were developed through chemical conjugation of a near-infrared (NIR) dye to the poly(ester) end by click chemistry. This strategy was tried for micelles with poly(ε-caprolactone) (PCL) or poly(α-benzyl carboxylate-ε-caprolactone) (PBCL) cores. The surface of both micelles was also modified with the breast cancer targeting peptide, P18-4. The results showed the positive contribution of PBCL over PCL core on micellar thermodynamic and kinetic stability as well as accumulation in primary orthotopic MDA-MB-231 tumors within 4–96 h following intravenous administration in mice. This was in contrast to in vitro studies where better uptake of PEO-PCL versus PEO-PBCL micelles …

Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique drug …

Efficient Synthesis Of Cn2097 Using In Situ Activation Of Sulfhydryl Group, Shaban Darwish, Keykavous Parang, John Marshall, Dennis J. Goebel, Rakesh Tiwari

Pharmacy Faculty Articles and Research

CN2097 (R₇Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR₇ and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR₇) …

The Motor Cortical Representation Of A Muscle Is Not Homogeneous In Brain Connectivity, Jo Armour Smith, Alaa Albishi, Sarine Babikian, Skulpan Asavasopon, Beth E. Fisher, Jason Kutch

Physical Therapy Faculty Articles and Research

Functional connectivity patterns of the motor cortical representational area of single muscles have not been extensively mapped in humans, particularly for the axial musculature. Functional connectivity may provide a neural substrate for adaptation of muscle activity in axial muscles that have both voluntary and postural functions. The purpose of this study was to combine brain stimulation and neuroimaging to both map the cortical representation of the external oblique (EO) in primary motor cortex (M1) and supplementary motor area (SMA), and to establish the resting-state functional connectivity associated with this representation. Motor evoked potentials were elicited from the EO muscle in …

Effects Of Phosphodiesterase 3a Modulation On Murine Cerebral Microhemorrhages, Rachita K. Sumbria, Vitaly Vasilevko, Mher Mahoney Grigoryan, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development.

Methods: The effect of PDE3A pathway inhibition was studied in the inflammation-induced and …

Source Localization Of Brain States Associated With Canonical Neuroimaging Postures, Michael Lifshitz, Robert T. Thibault, Raquel R. Roth, Amir Raz

Psychology Faculty Articles and Research

Cognitive neuroscientists rarely consider the influence that body position exerts on brain activity; yet, postural variation holds important implications for the acquisition and interpretation of neuroimaging data. Whereas participants in most behavioral and EEG experiments sit upright, many prominent brain imaging techniques (e.g., fMRI) require participants to lie supine. Here we demonstrate that physical comportment profoundly alters baseline brain activity as measured by magnetoencephalography (MEG)—an imaging modality that permits multipostural acquisition. We collected resting-state MEG data from 12 healthy participants in three postures (lying supine, reclining at 45°, and sitting upright). Source-modeling analysis revealed a broadly distributed influence of posture …

Tumor Necrosis Factor Α Inhibition For Alzheimer's Disease, Rudy Chang, Kei-Lwun Yee, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

Efficacy Of Electromyography And The Dead Bug Exercise, Taylor M. Scavo, Rachel C. Cooklin, Erika N. Faria, Madeline L. Johnson, Eric Sternlicht

Student Scholar Symposium Abstracts and Posters

The Dead Bug exercise is performed in physical therapy clinics to restore lumbar spine stability and core strength in patients with lower back pain (LBP). The aim of this study was to evaluate the efficacy of using electromyography (EMG) feedback to enhance proper mechanics during the Dead Bug exercise. Sixteen healthy, college age students volunteered as subjects for the study. Subjects performed the Dead Bug (Fig. 1a.) with and without visual EMG cues and were given instructions on how to execute the exercise. Data was recorded using a BTS FREEEMG Analyzer and signal processed and data analyzed using the BTS …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild

Pharmacy Faculty Articles and Research

Background
The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns.

Methods
Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection …

Thujone Inhibits The Function Of Α7-Nicotinic Acetylcholine Receptors And Impairs Nicotine-Induced Memory Enhancement In One-Trial Passive Avoidance Paradigm, Ahmed Sultan, Keun-Hang Susan Yang, Dmytro Isaev, Eslam El Nebrisi, Nurulain Syed, Nadia Khan, Christopher F. Howarth, Bassem Sadek, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100 μM)-induced currents with an IC50 value of 24.7 μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca2+-dependent Cl- channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [125I] -bungarotoxin was not altered by thujone. Further experiments in SH-EP1 …

Neurofeedback Or Neuroplacebo?, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

This scientific commentary refers to ‘Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia’, by Schabus et al.. (doi:10.1093/brain/awx011).

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling …