Neuro-Ophthalmology

Areas of Research Focus

Visual correlates of neurodegenerative disease

Description

Our lab is investigating use of ocular biomarkers for assessing risk of neurodegenerative disease and monitoring treatment efficacy of various modalities intended to ameliorate disease progression. Specifically, our work has involved exploitation of pupillary responses as a means to assess both afferent and efferent neural pathways influenced by factors such as mood, neuroticism, sleep function and physical comorbidity associated with neurologic disease as measured by altered pupil function. Our work in Parkinson’s disease has shown that intrinsic retinal ganglion cells, which are important for appropriate circadian balance are abnormal in PD as noted by the relationship between ipRGC action and pupil function. Our future work involves assessment of how photoreceptors, including ipRGCs as well as rods and cones, contribute to circadian oscillation in two distinct ways, as oscillator components or as mediators of luminous flux that do not involve rhythmicity, a phenomenon termed masking. In mammals, light is the most important zeitgeber synchronizing circadian rhythm. Luminous flux can therefore impact human activity in two ways, either by synchronizing an endogenous oscillator, modulated through ipRGCs, which in turn operationalize diurnal activity via a zeitgeber pacemaker, or through masking. Further work will provide explanations as to how masking intersects with vision through alteration in pupillary responses.

Research Team

Bruce Gaynes O.D., PharmD 

Description

The Gaynes lab works in conjunction with the Edward Hines VA Hospital and encompasses appraisal of ocular markers of neurodegeneration and neurovascular abnormality. The focus of our clinical program involves use of pupillometry in conjunction with assessment of retinal vascular and neural morphology as prodromal diagnostic metrics of neurodegenerative disorders. Other research emphasis includes application of light therapy as a means to ameliorate symptoms associated with migraine disorders and sleep abnormality related to disorders such as Parkinson’s disease. Our lab is also developing tools to improve assessment of ocular hemorheology as applied to estimation of stroke risk and optimizing therapy for coagulopathy.

Research Team 

Bruce Gaynes O.D., PharmD

Publications

2021

  1. Gaynes BI, Zaffer A, Yousefzai R, Chazaro-Cortes M, Colletta K, Kletzel SL, Jost MB, Park Y, Chawla J, Albert MV, Xiao T. Variable abnormality of the melanopsin-derived portion of the pupillary light reflex (PLR) in patients with Parkinson's disease (PD) and parkinsonism features. Neurological Sciences. 2021 May; doi: 10.1007/s10072-021-05245-8. Epub ahead of print. PMID: 33945034.

Use of light therapy to ameliorate debilitating effects migraine and sleep abnormality associated with Parkinson’s disease.

Description

The Gaynes lab works in conjunction with the Edward Hines VA Hospital and encompasses appraisal of ocular markers of neurodegeneration and neurovascular abnormality. The focus of our clinical program involves use of pupillometry in conjunction with assessment of retinal vascular and neural morphology as prodromal diagnostic metrics of neurodegenerative disorders. Other research emphasis includes application of light therapy as a means to ameliorate symptoms associated with migraine disorders and sleep abnormality related to disorders such as Parkinson’s disease. Our lab is also developing tools to improve assessment of ocular hemorheology as applied to estimation of stroke risk and optimizing therapy for coagulopathy.

Research Team

Bruce Gaynes O.D., PharmD

Publications

2021

  1. Tabashum T, Zaffer A, Yousefzai R, Colletta K, Jost MB, Park Y, Chawla J, Albert MV, Gaynes BI, Xiao T. Detection of Parkinson's Disease through Automated Pupil Tracking of the Post-illumination Pupillary Response. Frontiers in Medicine. 2021 March; 8: 316. https://doi.org/10.3389/fmed.2021.645293. PMID: 33842509. PMCID: PMC8026862.

Assessment of ocular hemorheology as a metric of stroke risk.

Description

The application of in-vivo conjunctival microvascular hemorheological determination offers the potential to impact numerous attributes of cardiovascular disease management not previously accessible including diagnosis and optimization of pharmacotherapy intervention for treatment of coagulopathy associated with various disorders including renal disease, diabetes mellitus and, recently SARS CoV-2. The purpose of the present study is to optimize an imaging paradigm for conjunctival microvascular blood flow study, define biologic variability of conjunctival rheology in a normative population sample and exploit our understanding of conjunctival hemorheology to elucidate in-vivo rheologic biomarkers of cardiac disease.  We intend to test the hypothesis that metrics of in-vivo conjunctival hemorheology are valid predictors of cardiac pathophysiology among individuals with heart failure. This project will establish normative conjunctival hemorheological metrics useful in future clinical studies examining microvascular abnormality in various disease cohorts.

Research Team 

Bruce Gaynes O.D., PharmD

 

Publications

2022

  1. Gaynes BI, Shapiro MD, Augustine AS, Xu Y, Lin Y, Mirbod P, Dieter RS, Cheng Y, Wu M, Venkataraman H, Gao Y, Petrov P, Xu J. Hierarchical data visualization of experimental erythrocyte aggregation employing cross correlation and optical flow applications. Microvascular Research. 2022 May; 143:104386. doi: 10.1016/j.mvr.2022.104386. Epub ahead of print. PMID: 35623407.

2021

  1. Patel N, Duong S, Mirbod P, Xu J. Gaynes BI. A meta-analysis of variability in conjunctival microvascular hemorheology metrics. Microvascular Research. 2022 February; 142:104340. doi: 10.1016/j.mvr.2022.104340. PMID: 35151720.

Experimental autoimmune neuritis and polyneuropathy

Description

 

Research Team 

Evan Stubbs Jr. Ph.D.

Simon Kaja Ph.D.

Publications

2020

  1. Stubbs Jr. EB. Targeting the blood-nerve barrier for management of immune-mediated peripheral neuropathies. Experimental Neurology. 2020 June; 331: 113385. doi: 10.1016/j.expneurol.2020.113385. PMID: 32562668.

2019

  1. Henry M, Johnson C, Ghadiali L, Raiji V. Horner's Syndrome Following Varicella Vaccination. Neuro-Ophthalmology. 2019 February; 44(4): 267-269. https://doi.org/10.1080/01658107.2019.1583759.    
  2. Stubbs Jr. EB, Fisher MA, Miller CM, Jelinek C, Butler J, McBurney C, Collins EG. Randomized controlled trial of physical exercise in diabetic Veterans with length-dependent distal symmetric polyneuropathy. Frontiers in Neuroscience. 2019 February; 13: 51. doi: 10.3389/fnins.2019.00051. PMCID: PMC6379046.
  3. Kouzoukas DE, Schreiber JA, Tajuddin NF, Kaja S, Neafsey EJ, Kim HY, Collins MA. PARP inhibition in vivo blocks alcohol-induced brain neurodegeneration and neuroinflammatory cytosolic phospholipase A2 elevations. Neurochemistry International. 2019 October; 129: 104497. doi: 10.1016/j.neuint.2019.104497. PMCID: PMC6760246.

2018

  1. Ragauskas S, Kielczewski E, Vance J, Kaja S, Kalesnykas G. In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model. Journal of Visualized Experiments. 2018 January; 131: 56173. doi: 10.3791/56173. PMCID: PMC5908670.

2017

  1. Huang J, Romero-Suarez S, Lara N, Mo C, Kaja S, Brotto L, Dallas SL, Johnson ML, Jähn K, Bonewald LF, Brotto M. Crosstalk between MLO-Y4 osteocytes and C2C12 muscle cells is mediated by the Wnt/β-catenin pathway. JBMR Plus. 2017 October; 1(2): 86-100. doi: 10.1002/jbm4.10015. PMCID: PMC5667655. 
  2. Sandoval A, Duran P, Gandini MA, Andrade A, Almanza A, Kaja S, Felix R. Regulation of L-type CaV1.3 channel activity and insulin secretion by the cGMP-PKG signaling pathway. Cell Calcium. 2017 September; 66: 1-9. doi: 10.1016/j.ceca.2017.05.008. PMCID: PMC5776030.
  3. Langert KA, Goshu B, Stubbs Jr. EB. Attenuation of experimental autoimmune neuritis with locally administered lovastatin-encapsulating PLGA nanoparticles. Journal of Neurochemistry. 2017 January; 140(2): 334-346. doi: 10.1111/jnc.13892. PMCID: PMC5225029. 

2016

  1. Means JC, Gerdes BC, Kaja S, Sumien N, Payne AJ, Stark DA, Borden PK, Price JL, Koulen P. Caspase-3-Dependent Proteolytic Cleavage of Tau Causes Neurofibrillary Tangles and Results in Cognitive Impairment During Normal Aging. Neurochem Res. 2016 May; 41: 2278-2288. doi: 10.1007/s11064-016-1942-9. PMCID: PMC4965284.
  2. Richter F, Koulen P, Kaja S. N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release. Scientific Reports. 2016 March; 6: 23481. doi: 10.1038/srep23481. PMCID: PMC4804239.
  3. Ni A, Yang T, Mesnard-Hoaglin NA, Gutierreza R, Stubbs Jr. EB, McGuire SO, Sanders VM, Jones KJ, Foecking EM, Xin JP. Th17 cell response in SOD1G93A mice following motor nerve injury. Mediators of Inflammation. 2016 February; 2016: 6131234. doi: 10.1155/2016/6131234. PMCID: PMC4852359.

2015

  1. Ostrowski RA, Bussey MR, Shayesteh Y, Jay WM. Rituximab in the Treatment of Thyroid Eye Disease: A Review. Neuro-Ophthalmology. 2015 June; 39(3): 109-115. doi: 10.3109/01658107.2015.1039140. PMCID: PMC5123122.
  2. Calik MW, Shankarappa SA, Langert KA, Stubbs Jr. EB. Forced-exercise preconditioning attenuates experimental autoimmune neuritis by altering Th1 lymphocyte composition and egress. ASN Neuro. 2015 July; 7(4): 1-11. https://doi.org/10.1177/1759091415595726. PMCID: PMC4550317.

2014

  1. Lovera L, JAY W.M., Biller J. Horner Syndrome in a Case of Neuromyelitis Optica. Neuro-Ophthalmology. 2014 February; 38(2): 78-81. doi: 10.3109/01658107.2013.856027. PMCID: PMC5122924.
  2. Irvine D, Zemke A, Pusateri G, Gerlach L, Chun R, JAY, WM. Tablet and smartphone accessibility features in the low vision rehabilitation. Neuro-Ophthalmology. 2014 March; 38(2): 53-59. doi: 10.3109/01658107.2013.874448. PMCID: PMC5123149.
  3. Ostrowski RA, Bussey MR., Tehrani R, Jay, WM. Biologic therapy for the treatment of giant cell arteritis. Neuro-Ophthalmology. 2014 April; 38(3): 107-112. doi: 10.3109/01658107.2014.883635. PMCID: PMC5123077.
  4. Langert KA, Pervan CL, Stubbs Jr. EB. Novel role of Cdc42 and RalA GTPases in tumor necrosis factor-α mediated secretion of CCL2. Small GTPases. 2014 May; 5(3): 29260. doi: 10.4161/sgtp.29260. PMCID: PMC4205150.

2013

  1. Langert KA, Von Zee CL, Stubbs Jr. EB. Cdc42 GTPases facilitate Tumor Necrosis Factor-α mediated secretion of CCL2 from peripheral nerve microvascular endoneurial endothelial cells. Journal of the Peripheral Nervous System. 2013 September; 18(3):199-208. doi: 10.1111/jns5.12032. PMCID: PMC3785369. 
  2. Langert KA, Von Zee CL, Stubbs Jr. EB. Tumor Necrosis Factor-α enhances CCL2 and ICAM-1 expression in peripheral nerve vascular endoneurial endothelial cells. ASN Neuro. 2013 February; 5(1): e00104. doi: 10.1042/AN20120048. PMCID: PMC3565377. 

2012

  1. Calik MW, Shankarappa SA, Stubbs Jr. EB. Forced-exercise attenuates experimental autoimmune neuritis. Neurochemistry International. 2012 July; 61(2): 141-145. doi: 10.1016/j.neuint.2012.04.023. PMID: 22569066.