The use of the vaccinia virus complement control protein (VCP) in the rat retina

Autor: Krisztina Valter, Riccardo Natoli, Yvette Wooff, Jan Provis, Nilisha Fernando, Tanja Racic
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Photoreceptors
0301 basic medicine
Retinal degeneration
Complement Inhibitors
Sensory Receptors
Light
genetic structures
Physiology
Complement System
Social Sciences
lcsh:Medicine
Biochemistry
Photoreceptor cell
chemistry.chemical_compound
Complement inhibitor
Animal Cells
Immune Physiology
Medicine and Health Sciences
Psychology
Medicine
lcsh:Science
Complement Activation
Neurons
Immune System Proteins
Multidisciplinary
Cell Death
biology
Retinal Degeneration
3. Good health
Cell biology
Protein Transport
medicine.anatomical_structure
Cell Processes
Retinal Disorders
Sensory Perception
Anatomy
Cellular Types
medicine.symptom
Oxidation-Reduction
Research Article
Signal Transduction
Ocular Anatomy
Immunology
Inflammation
Hemolysis
Retina
Viral Proteins
03 medical and health sciences
Ocular System
Animals
business.industry
lcsh:R
Biology and Life Sciences
Proteins
Afferent Neurons
Retinal
Cell Biology
medicine.disease
eye diseases
Rats
Complement system
Ophthalmology
030104 developmental biology
chemistry
Immune System
Cellular Neuroscience
biology.protein
Eyes
lcsh:Q
sense organs
business
Head
Neuroscience
Complement control protein
Zdroj: PLoS ONE, Vol 13, Iss 3, p e0193740 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: The complement system is highly implicated in both the prevalence and progression of Age-Related Macular Degeneration (AMD). Complement system inhibitors therefore have potential therapeutic value in managing excessive activation of the complement pathways in retinal degenerations. The vaccinia virus complement control protein (VCP) has been shown to be effective as a complement inhibitor in neuroinflammatory models including traumatic brain injury and spinal cord injury. We aimed to investigate the potential of VCP as a therapeutic molecule for retinal degenerations. In this study, we investigated the effect, localisation and delivery of VCP to the rodent retina. Complement inhibition activity of VCP was tested using a hemolytic assay. Photoreceptor cell death, inflammation and retinal stress were assayed to determine if any retinal toxicity was induced by an intravitreal injection of VCP. The effect of VCP was investigated in a model of photo-oxidative retinal degeneration. Localisation of VCP after injection was determined using a fluorescein-tagged form of VCP, as well as immunohistochemistry. Finally, a copolymer resin (Elvax) was trialled for the slow-release delivery of VCP to the retina. We found that a dose equivalent to 20μg VCP when intravitreally injected into the rat eye did not cause any photoreceptor cell death or immune cell recruitment, but led to an increase in GFAP. In photo-oxidative damaged retinas, there were no differences in photoreceptor loss, retinal stress (Gfap) and inflammation (Ccl2 and C3) between VCP and saline-injected groups; however, Jun expression was reduced in VCP-treated retinas. After VCP was injected into the eye, it was taken up in all layers of the retina but was cleared within 1-3 hours of delivery. This study indicates that a method to sustain the delivery of VCP to the retina is necessary to further investigate the effect of VCP as a complement inhibitor for retinal degenerations.
Databáze: OpenAIRE
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