Intravitreal Neuroglobin Mitigates Primate Experimental Glaucomatous Structural Damage in Association with Reduced Optic Nerve Microglial and Complement 3-Astrocyte Activation

Current management of glaucomatous optic neuropathy is limited to intraocular pressure control. Neuroglobin (Ngb) is an endogenous neuroprotectant expressed in neurons and astrocytes. We recently showed that exogenous intravitreal Ngb reduced inflammatory cytokines and microglial activation in a rod...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2023-06, Vol.13 (6), p.961
Main Authors: Chan, Anita S Y, Tun, Sai B B, Lynn, Myoe N, Ho, Candice, Tun, Tin A, Girard, Michaël J A, Sultana, Rehena, Barathi, Veluchamy A, Aung, Tin, Aihara, Makoto
Format: Article
Language:English
Subjects:
Animals
Astrocytes
astrogliosis
Caspase-3
complement 3
Complement activation
Complement C3
Cytokines
Gene therapy
Glaucoma
Glaucoma - drug therapy
glaucomatous optic neuropathy
Gliosis
Globular proteins
Health aspects
Histology
Hypoxia
Immunohistochemistry
Inflammation
Ischemia
Laboratory animals
Macaca fascicularis
Microglia
microgliosis
Microspheres
Monkeys & apes
Neuroglobin
Neuroglobin - administration & dosage
Neuroglobin - therapeutic use
Neuroprotection
Neuroprotective agents
Ophthalmology
Optic Disk
Optic nerve
Optic neuropathy
Optics
Physiological aspects
Primates
Proteins
Tomography
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Summary:Current management of glaucomatous optic neuropathy is limited to intraocular pressure control. Neuroglobin (Ngb) is an endogenous neuroprotectant expressed in neurons and astrocytes. We recently showed that exogenous intravitreal Ngb reduced inflammatory cytokines and microglial activation in a rodent model of hypoxia. We thus hypothesised that IVT-Ngb may also be neuroprotective in experimental glaucoma (EG) by mitigating optic nerve (ON) astrogliosis and microgliosis as well as structural damage. In this study using a microbead-induced model of EG in six Cynomolgus primates, optical coherence imaging showed that Ngb-treated EG eyes had significantly less thinning of the peripapillary minimum rim width, retinal nerve fibre layer thickness, and ON head cupping than untreated EG eyes. Immunohistochemistry confirmed that ON astrocytes overexpressed Ngb following Ngb treatment. A reduction in complement 3 and cleaved-caspase 3 activated microglia and astrocytes was also noted. Our findings in higher-order primates recapitulate the effects of neuroprotection by Ngb treatment in rodent EG studies and suggest that Ngb may be a potential candidate for glaucoma neuroprotection in humans.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom13060961