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Wei Z.Z.,Emory University | Wei Z.Z.,Center for Visual and Neurocognitive Rehabilitation | Yu S.P.,Emory University | Yu S.P.,Center for Visual and Neurocognitive Rehabilitation | And 7 more authors.
Cellular and Molecular Neurobiology | Year: 2014

Stem cell transplantation therapy has provided promising hope for the treatment of a variety of neurodegenerative disorders. Among challenges in developing disease-specific stem cell therapies, identification of key regulatory signals for neuronal differentiation is an essential and critical issue that remains to be resolved. Several lines of evidence suggest that JNK, also known as SAPK, is involved in neuronal differentiation and neural plasticity. It may also play a role in neurite outgrowth during neuronal development. In cultured mouse embryonic stem (ES) cells, we test the hypothesis that the JNK pathway is required for neuronal differentiation. After neural induction, the cells were plated and underwent differentiation for up to 5 days. Western blot analysis showed a dramatic increase in phosphorylated JNKs at 1-5 days after plating. The phosphorylation of JNK subsequently induced activation of STAT1 and STAT3 that lead to expressions of GAP-43, neurofilament, βIII-tubulin, and synaptophysin. NeuN-colabelled with DCX, a marker for neuroblast, was enhanced by JNK signaling. Neuronal differentiation of ES cells was attenuated by treatment with SP600125, which inhibited the JNK activation and decreased the activation of STAT1 and STAT3, and consequently suppressed the expressions of GAP-43, neurofilament, βIII-tubulin, and the secretion of VEGF. Data from immunocytochemistry indicated that the nuclear translocation of STAT3 was reduced, and neurites of ES-derived neurons were shorter after treatment with SP600125 compared with control cells. These results suggest that the JNK-STAT3 pathway is a key regulator required for early neuronal differentiation of mouse ES cells. Further investigation on expression of JNK isoforms showed that JNK-3 was significantly upregulated during the differentiation stage, while JNK-1 and JNK-2 levels decreased. Our study provided interesting information on JNK functions during ES cell neuronal differentiation. © 2014 Springer Science+Business Media.


PubMed | VA Palo Alto Health Care System, Center for Visual and Neurocognitive Rehabilitation and Emory University
Type: Journal Article | Journal: Military medicine | Year: 2017

Eye care in the Veterans Affairs Health Care System is challenged with increasing demand and higher prevalence of patients with complex ocular conditions. Understanding factors that impact eye care productivity and access is necessary for appropriate allocation of resources. The purpose of this study was to determine the impact of various eye clinic personnel on eye care provider productivity and patient access.Utilizing data from the Veterans Health Administration National Data Warehouse, workload and level of staffing were analyzed. Trends in the data were analyzed using descriptive and regression analyses employing both linear and curve fitting modeling methods.There was a significant positive correlation between ophthalmology technicians and ophthalmologist productivity (p < 0.001), number of unique patients seen per year per provider (p = 0.047), and total yearly number of office visits per provider (p < 0.001). Similarly, there was a significant positive correlation between number of ophthalmology residents and productivity (p = 0.046) and number of clinic visits per provider (p < 0.001) but not the number of unique patients seen. Positive correlation was found between optometry technicians and the number of unique patients seen by optometrists (p = 0.041) and total number of clinic visits per provider (p < 0.001) but not optometrist productivity. No significant correlations were present for nurses, nurse practitioners, physician assistants, or clerical staff.Eye care technicians provide a cost-effective multiplier effect for provider productivity, especially in ophthalmology clinics, allowing significant increases in total clinic visits and number of unique patients seen per year.


Stone R.A.,University of Pennsylvania | Cohen Y.,University of Pennsylvania | McGlinn A.M.,University of Pennsylvania | Davison S.,University of Pennsylvania | And 6 more authors.
Investigative Ophthalmology and Visual Science | Year: 2016

PURPOSE. The hypothesis that outdoor exposure might protect against myopia has generated much interest, although available data find only modest clinical efficacy. We tested the effect of outdoor rearing on form-deprivation myopia in chicks, a myopia model markedly inhibited by high-intensity indoor laboratory lighting. METHODS. Unilaterally goggled cohorts of White Leghorn chicks were maintained in a species- appropriate, outdoor rural setting during daylight hours to the extent permitted by weather. Control chicks were reared indoors with incandescent lighting. Besides ocular refraction and ultrasound, we determined dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content in retina and vitreous and measured mRNA expression levels of selected clock and circadian rhythm-related genes in the retina/RPE. RESULTS. Myopia developed in the goggled eyes of all cohorts. Whereas outdoor rearing lessened myopia by 44% at 4 days, a protective effect was no longer evident at 11 days. Outdoor rearing had no consistent effect on retinal or vitreous content of dopamine or DOPAC. Conforming to prior data on form-deprivation myopia, retina and vitreous levels of DOPAC were reduced in goggled eyes. Compared with contralateral eyes, the retinal expression of clock and circadian rhythm-related genes was modestly altered in myopic eyes of chicks reared indoors or outdoors. CONCLUSIONS. Outdoor rearing of chicks induces only a partial decrease of goggle-induced myopia that is not maintained, without evidence that retinal dopamine metabolism accounts for the partial myopia inhibition under these outdoor conditions. Although modest, alterations in retinal gene expression suggest that studying circadian signals might be informative for understanding refractive mechanisms. © 2016 Association for Research in Vision and Ophthalmology Inc. All rights reserved.


Chasan J.E.,Emory University | Delaune B.,Center for Visual and Neurocognitive Rehabilitation | Maa A.Y.,Emory University | Maa A.Y.,Atlanta Medical Center | And 2 more authors.
JAMA Ophthalmology | Year: 2014

IMPORTANCE: Telemedicine is a useful clinical method to extend health care to patients with limited access. Minimal information exists on the subsequent effect of telemedicine activities on eye care resources. OBJECTIVE: To evaluate the effect of a community-based diabetic teleretinal screening program on eye care use and resources. DESIGN, SETTING, AND PARTICIPANTS: The current studywas a retrospective medical record review of patients who underwent diabetic teleretinal screening in the community-based clinics of the Atlanta Veterans Affairs Medical Center from October 1, 2008, through March 31, 2009, and who were referred for an ophthalmic examination in the eye clinic. EXPOSURES: Clinical medical records were reviewed for a 2-year period after patients were referred from teleretinal screening. The following information was collected for analysis: patient demographics, referral and confirmatory diagnoses, ophthalmology clinic visits, diagnostic procedures, surgical procedures, medications, and spectacle prescriptions. MAIN OUTCOMES AND MEASURES: The accuracy between referring and final diagnoses and the eye care resources that were used in the care of referred patients. RESULTS: The most common referral diagnoses were nonmacular diabetic retinopathy (43.2%), nerve-related disease (30.8%), lens or media opacity (19.1%), age-related macular degeneration (12.9%), and diabetic macular edema (5.6%). The percentage of agreement among these 5 visually significant diagnoses was 90.4%, with a total sensitivity of 73.6%. Diabetic macular edema required the greatest number of ophthalmology clinic visits, diagnostic tests, and surgical procedures. Using Medicare cost data estimates, the mean cost incurred during a 2-year period per patient seen in the eye clinic was approximately $1000. CONCLUSIONS AND RELEVANCE: Although a teleretinal screening program can be accurate and sensitive for multiple visually significant diagnoses, measurable resource burdens should be anticipated to adequately prepare for the associated increase in clinical care. Copyright 2014 American Medical Association. All rights reserved.


Kelly R.,Georgia Institute of Technology | Mizelle J.C.,Georgia Institute of Technology | Mizelle J.C.,Center for Visual and Neurocognitive Rehabilitation | Wheaton L.A.,Georgia Institute of Technology
Neuropsychologia | Year: 2015

Prior work has demonstrated that perspective and handedness of observed actions can affect action understanding differently in right and left-handed persons, suggesting potential differences in the neural networks underlying action understanding between right and left-handed individuals. We sought to evaluate potential differences in these neural networks using electroencephalography (EEG). Right- and left-handed participants observed images of tool-use actions from egocentric and allocentric perspectives, with right- and left-handed actors performing the actions. Participants judged the outcome of the observed actions, and response accuracy and latency were recorded. Behaviorally, the highest accuracy and shortest latency was found in the egocentric perspective for right- and left-handed observers. Handedness of subject showed an effect on accuracy and latency also, where right-handed observers were faster to respond than left-handed observers, but on average were less accurate. Mu band (8-10. Hz) cortico-cortical coherence analysis indicated that right-handed observers have coherence in the motor dominant left parietal-premotor networks when looking at an egocentric right or allocentric left hands. When looking in an egocentric perspective at a left hand or allocentric right hand, coherence was lateralized to right parietal-premotor areas. In left-handed observers, bilateral parietal-premotor coherence patterns were observed regardless of actor handedness. These findings suggest that the cortical networks involved in understanding action outcomes are dependent on hand dominance, and notably right handed participants seem to utilize motor systems based on the limb seen performing the action. The decreased accuracy for right-handed participants on allocentric images could be due to asymmetrical lateralization of encoding action and motoric dominance, which may interfere with translating allocentric limb action outcomes. Further neurophysiological studies will determine the specific processes of how left- and right-handed participants understand actions. © 2015 Elsevier Ltd.


PubMed | Center for Visual and Neurocognitive Rehabilitation, University of Illinois at Chicago, Emory University and Georgia Institute of Technology
Type: | Journal: Experimental eye research | Year: 2016

Low-level electrical stimulation to the eye has been shown to be neuroprotective against retinal degeneration in both human and animal subjects, using approaches such as subretinal implants and transcorneal electrical stimulation. In this study, we investigated the benefits of whole-eye electrical stimulation (WES) in a rodent model of retinitis pigmentosa. Transgenic rats with a P23H-1 rhodopsin mutation were treated with 30min of low-level electrical stimulation (4Aat 5Hz; n=10) or sham stimulation (Sham group; n=15), twice per week, from 4 to 24 weeks of age. Retinal and visual functions were assessed every 4 weeks using electroretinography and optokinetic tracking, respectively. At the final time point, eyes were enucleated and processed for histology. Separate cohorts were stimulated once for 30min, and retinal tissue harvested at 1h and 24h post-stimulation for real-time PCR detection of growth factors and inflammatory and apoptotic markers. At all time-points after treatment, WES-treated rat eyes exhibited significantly higher spatial frequency thresholds than untreated eyes. Inner retinal function, as measured by ERG oscillatory potentials (OPs), showed significantly improved OP amplitudes at 8 and 12 weeks post-WES compared to Sham eyes. Additionally, while photoreceptor segment and nuclei thicknesses in P23H-1 rats did not change between treatment groups, WES-treated eyes had significantly greater numbers of retinal ganglion cell nuclei than Sham eyes at 20 weeks post-WES. Gene expression levels of brain-derived neurotrophic factor (BDNF), caspase 3, fibroblast growth factor 2 (FGF2), and glutamine synthetase (GS) were significantly higher at 1h, but not 24h after WES treatment. Our findings suggest that WES has a beneficial effect on visual function in a rat model of retinal degeneration and that post-receptoral neurons may be particularly responsive to electrical stimulation therapy.


PubMed | Kosin University, University of Louisville, Stanford University, Center for Visual and Neurocognitive Rehabilitation and Emory University
Type: Journal Article | Journal: Translational vision science & technology | Year: 2015

To investigate the integration of subretinal implants containing full-depth perforations of various widths with rat and pig retina across weeks of implantation.In transgenic P23H rhodopsin line 1 (TgP23H-1) rats and wild-type (WT) pigs, we examined four subretinal implant designs: solid inactive polymer arrays (IPA), IPAs with 5- or 10-m wide perforations, and active bipolar photovoltaic arrays (bPVA) with 5-m perforations. We surgically placed the implants into the subretinal space using an external approach in rats or a vitreoretinal approach in pigs. Implant placement in the subretinal space was verified with optical coherence tomography and retinal perfusion was characterized with fluorescein angiography. Rats were sacrificed 8 or 16 weeks post-implantation (wpi) and pigs 2, 4, or 8 wpi, and retinas evaluated at the light microscopic level.Regardless of implant design, retinas of both species showed normal vasculature. In TgP23H-1 retinas implanted with 10-m perforated IPAs, inner nuclear layer (INL) cells migrated through the perforations by 8 wpi, resulting in significant INL thinning by 16 wpi. Additionally, these retinas showed greater pseudo-rosette formation and fibrosis compared with retinas with solid or 5-m perforated IPAs. TgP23H-1 retinas with bPVAs showed similar INL migration to retinas with 5-m perforated IPAs, with less fibrosis and rosette formation. WT pig retina with perforated IPAs maintained photoreceptors, showed no migration, and less pseudo-rosette formation, but more fibrosis compared with implanted TgP23H-1 rat retinas.In retinas with photoreceptor degeneration, solid implants, or those with 5-m perforations lead to the best biocompatibility.


Sathian K.,Emory University | Sathian K.,Center for Visual and Neurocognitive Rehabilitation
Journal of Neurophysiology | Year: 2016

Haptic sensing of objects acquires information about a number of properties. This review summarizes current understanding about how these properties are processed in the cerebral cortex of macaques and humans. Nonnoxious somatosensory inputs, after initial processing in primary somatosensory cortex, are partially segregated into different pathways. A ventrally directed pathway carries information about surface texture into parietal opercular cortex and thence to medial occipital cortex. A dorsally directed pathway transmits information regarding the location of features on objects to the intraparietal sulcus and frontal eye fields. Shape processing occurs mainly in the intraparietal sulcus and lateral occipital complex, while orientation processing is distributed across primary somatosensory cortex, the parietal operculum, the anterior intraparietal sulcus, and a parieto-occipital region. For each of these properties, the respective areas outside primary somatosensory cortex also process corresponding visual information and are thus multisensory. Consistent with the distributed neural processing of haptic object properties, tactile spatial acuity depends on interaction between bottom-up tactile inputs and topdown attentional signals in a distributed neural network. Future work should clarify the roles of the various brain regions and how they interact at the network level. © 2016 the American Physiological Society.


Chakraborty R.,Emory University | Chakraborty R.,Center for Visual and Neurocognitive Rehabilitation | Park H.N.,Emory University | Park H.N.,Center for Visual and Neurocognitive Rehabilitation | And 5 more authors.
Experimental Eye Research | Year: 2015

The ON pathway mutation in nob mice is associated with altered refractive development, and an increased susceptibility to form-deprivation (FD) myopia. In this study, we used mGluR6-/- mice, another ON pathway mutant, to determine whether the nob phenotype was due to the Nyx mutation or abnormal ON pathway transmission. Refractive development under a normal visual environment for mGluR6-/- and age-matched wild-type (WT) mice was measured every 2 weeks from 4 to 16 weeks of age. The response to monocular FD from 4 weeks of age was measured weekly in a separate cohort of mice. Refraction and ocular biometry were obtained using a photorefractor and optical coherence tomography. Retinas were harvested at 16 weeks, and analyzed for dopamine (DA) and DOPAC using high-performance liquid chromatography. Under normal conditions, mGluR6-/- mice were significantly more myopic than their WT controls (refraction at 12 weeks; WT: 9.40±0.16 D. , mGluR6-/-: 6.91±0.38 D). Similar to nob mice, two weeks of FD resulted in a significant myopic shift of-5.57±0.72 D in mGluR6-/- mice compared to-1.66±0.19 D in WT animals. No significant axial length changes were observed with either normal or FD visual conditions. At 16 weeks, mGluR6-/- retinas showed significantly lower DOPAC levels (111.2±33.0pg/mg) compared to their WT counterparts (197.5±11.2pg/mg). Retinal DA levels were similar between the different genotypes. Our results indicate that reduced retinal DA metabolism/turnover may be associated with increased susceptibility to myopia in mice with ON pathway defect mutations. © 2015.


PubMed | Center for Visual and Neurocognitive Rehabilitation and Emory University
Type: Journal Article | Journal: Investigative ophthalmology & visual science | Year: 2015

Our previous investigations showed that involuntary treadmill exercise is neuroprotective in a light-induced retinal degeneration mouse model, and it may act through activation of tropomyosin-related kinase B (TrkB) receptors. This study investigated whether voluntary running wheel exercise can be neuroprotective in an inheritable model of the retinal degenerative disease retinitis pigmentosa (RP), rd10 mice.Breeding pairs of rd10 and C57BL/6J mice were given free-spinning (active) or locked (inactive) running wheels. Pups were weaned into separate cages with their parents respective wheel types, and visual function was tested with ERG and a virtual optokinetic system at 4, 5, and 6 weeks of age. Offspring were killed at 6 weeks of age and retinal cross-sections were prepared for photoreceptor nuclei counting. Additionally, separate cohorts of active and inactive rd10 pups were injected daily for 14 days after eye opening with a selective TrkB receptor antagonist (ANA-12) or vehicle solution and assessed as described above.Mice in the rd10 active group exhibited significant preservation of visual acuity, cone nuclei, and total photoreceptor nuclei number. Injection with ANA-12 precluded the preservation of visual acuity and photoreceptor nuclei number in rd10 mice.Voluntary running partially protected against the retinal degeneration and vision loss that otherwise occurs in the rd10 mouse model of RP. This protection was prevented by injection of ANA-12, suggesting that TrkB activation mediates exercises preservation of the retina. Exercise may serve as an effective, clinically translational intervention against retinal degeneration.

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