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2015 ; 5
(ä): 18316
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Sustained intraocular VEGF neutralization results in retinal neurodegeneration in
the Ins2(Akita) diabetic mouse
#MMPMID26671074
Hombrebueno JR
; Ali IH
; Xu H
; Chen M
Sci Rep
2015[Dec]; 5
(ä): 18316
PMID26671074
show ga
Current therapies that target vascular endothelial growth factor (VEGF) have
become a mainstream therapy for the management of diabetic macular oedema. The
treatment involves monthly repeated intravitreal injections of VEGF inhibitors.
VEGF is an important growth factor for many retinal cells, including different
types of neurons. In this study, we investigated the adverse effect of multiple
intravitreal anti-VEGF injections (200?ng/?l/eye anti-mouse VEGF164, once every 2
weeks totalling 5-6 injections) to retinal neurons in Ins2(Akita) diabetic mice.
Funduscopic examination revealed the development of cotton wool spot-like lesions
in anti-VEGF treated Ins2(Akita) mice after 5 injections. Histological
investigation showed focal swellings of retinal nerve fibres with neurofilament
disruption. Furthermore, anti-VEGF-treated Ins2(Akita) mice exhibited impaired
electroretinographic responses, characterized by reduced scotopic a- and b-wave
and oscillatory potentials. Immunofluorescent staining revealed impairment of
photoreceptors, disruptions of synaptic structures and loss of amacrine and
retinal ganglion cells in anti-VEGF treated Ins2(Akita) mice. Anti-VEGF-treated
WT mice also presented mild amacrine and ganglion cell death, but no overt
abnormalities in photoreceptors and synaptic structures. At the vascular level,
exacerbated albumin leakage was observed in anti-VEGF injected diabetic mice. Our
results suggest that sustained intraocular VEGF neutralization induces retinal
neurodegeneration and vascular damage in the diabetic eye.