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Oxidative stress‐induced retinal damage is prevented by mild hypothermia in an ex vivo model of cultivated porcine retinas
Author(s) -
MuellerBuehl Ana M.,
Doepper Hannah,
Grauthoff Sven,
Kiebler Tobias,
Peters Laura,
Hurst José,
Kuehn Sandra,
BartzSchmidt Karl U.,
Dick H. Burkard,
Joachim Stephanie C.,
Schnichels Sven
Publication year - 2020
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.13731
Subject(s) - oxidative stress , ex vivo , retinal , retina , apoptosis , medicine , in vivo , hypothermia , programmed cell death , microglia , organ culture , microbiology and biotechnology , biology , endocrinology , immunology , in vitro , biochemistry , neuroscience , ophthalmology , inflammation
Background Hydrogen peroxide (H 2 O 2 ) can be used in vitro to simulate oxidative stress. In retinal organ cultures, H 2 O 2 induces strong neurodegeneration of the retina. It is known that oxidative stress plays a role in the development of several retinal diseases including glaucoma and ischemia. Thus, we investigated whether processes underlying oxidative stress can be prevented by hypothermia using an ex vivo organ culture model of porcine retinas. Methods Porcine retinal explants were cultivated for 5 and 8 days. Oxidative stress was induced via 300 μM H 2 O 2 on day 1 for 3 hours. Hypothermia treatment at 30°C was applied simultaneously with H 2 O 2 , for 3 hours. Retinal ganglion cells (RGCs), apoptosis, bipolar and cholinergic amacrine cells, microglia and macroglia were evaluated immunohistologically. Apoptosis rate was additionally analysed via western blot. Results Reduced apoptosis rates through hypothermia led to a preservation of RGCs ( P < .001). Amacrine cells were rescued after hypothermia treatment ( P = .17), whereas bipolar cells were only protected partly. Additionally, at 8 days, microglial response due to oxidative stress was completely counteracted via hypothermia ( P < .001). Conclusions H 2 O 2 induced strong degenerative processes in porcine retinas. The role of oxidative stress in the progression of retinal diseases makes this ex vivo organ culture model suitable to investigate new therapeutic approaches. In the present study, the damaging effect of H 2 O 2 to several retinal cell types was counteracted or strongly alleviated through hypothermia treatment. Especially RGCs, which are affected in glaucoma disease, were protected due to a reduced apoptosis rate through hypothermia.