Day 1 :
National Institutes of Health, USA
Time : 09:30-10:00
Chi-Chao Chan, M.D. is the chief of Immunopathology Section, Laboratory of Immunology and the Head of Histology Core at the National Eye Institute (NEI), National Institutes of Health (NIH). In 1967, Dr. Chan graduated from Chungzhan Medical College (now known as Sun Yat-sen University) in Guangzhou, China. She earned her A.B. in 1972 and M.D. in 1975 at Johns Hopkins University. Following medical school, she completed her medical internship at Maimonides Medical Center in New York and ophthalmology residency at Stanford University Medical Center. Continuing her educational enrichment, Dr. Chan completed two post-doctoral fellowships in ophthalmic pathology at the Wilmer Ophthalmological Institute in 1982, and clinical ocular immunology/uveitis at the NEI in 1985. She is a board certified ophthalmologist and obtained a license of Clinical Laboratory Improvement Act (CLIA), certifying her in clinical laboratory diagnostics in ophthalmic pathology and molecular pathology. Dr. Chan is a world expert in intraocular lymphoma, immunopathology of uveitis, molecular pathology of age-related macular degeneration (AMD), ocular lymphoma and von Hippel-Lindau disease.rn
Age-related macular degeneration (AMD), the leading cause of irreversible central blindness in the elderly, is characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium, which is sometimes accompanied by choroidal neovascularization. Development of AMD is contingent on both environmental and genetic risk factors, the strongest being advanced age. With normal aging, photoreceptors are steadily lost, Bruch’s membrane thickens, the choroid thins, and hard drusen may form in the periphery. The changes are characterized as kinetics between homeostasis and allostasis. In AMD, many of these changes are exacerbated (chronic allostatic overload leading to pathology and disease); additionally, there is development of disease-specific factors such as macular soft drusen, geographic atrophy, and choroidal neovascularization. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis and physiological allostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 macrophage populations and activation of retinal microglia are observed and potentially contribute to tissue degeneration. In the chronic stage of allostatic overload, including oxidative stress, inflammasomes, and inflammatory cytokines (e.g., IL-1β, IL-17 and IL-18) wax and wane; retinal pigment epithelium and photoreceptors degenerate leading to programed cell death via apoptosis, autophagy, pyrotosis and/or necroptosis. Neovascularization may also develop. Therefore, the underlying mechanism of AMD involves homeostasis, allostasis, and allostatic overload, which all depend primarily on aging, inflammation, degeneration, atrophy, and neovascularization.
Autism Research Institute, USA
Keynote: Brainstem hypothesis for autism
Time : 10:00-10:30
Woody R McGinnis was educated at Dartmouth College and the University of Colorado, USA. After volunteer work in rural Peru, his general practice in Arizona included treatment of many children with autism. McGinnis commenced full-time research in autism in 2001 under the auspices of the Autism Research Institute, San Diego. In 2009, the publication of ‘Neurotoxic Brainstem Impairment as Proposed Threshold Event in Autistic Regression’ by CRC Press as a chapter in Autism: Oxidative Stress, Inflammation and Immune Abnormalities established McGinnis as a leading thinker in brainstem and autism. He has worked closely with the Autism Tissue Program and the University of Maryland Brain and Tissue Bank to enhance the collection of brainstem, including preservation of midline structures such as NTS.
Site-specific impairment of a small brainstem structure, nucleus tractus solitarius (NTS), is a potential break-through finding in the understanding of autistic spectrum disorder (ASD). NTS serves as initial central synapse for most sensory information from the viscera, and a broad set of unusual physical findings that associate with the diagnostic behaviors of ASD are explicable on the basis of reduced visceral afference. An exaggerated inflammatory response in ASD associates significantly with aberrant behaviors, and parallels the observation of increased inflammation after experimental splenic deafferentation. Likewise, deafferentation of the laryngeal viscera of animals results in reduced glottal closing force, proposed mechanism for our finding of whisper in association with autistic vocal regression. Experimental impairment of NTS results in depressed motor and secretory function of the gastrointestinal tract, prominent in ASD. Hypoperfusion of extensive brain regions with \\\\\\\"global dysregulation\\\\\\\" of cerebral blood-flow (CBF) is well-documented in ASD, and might be expected to alter development and integrated function of higher regions of brain. Animal experiments show that NTS is important in autoregulation of CBF, and that artificial stimulation of NTS increases CBF. An unusual vascular microanatomy is seen to confer a dual vulnerability of NTS to injury via hypoxia but also to toxins from the bloodstream that tend to concentrate preferentially in regions of brainstem such as NTS that are unprotected by BBB. Hence, we consider specific hypoxic events and common toxic exposures that could act together or separately in order to trigger ASD at varied points in the neurodevelopmental sequence.