Hypothermia protects retinal ganglion cells against hypoxia‐induced cell death in a retina organ culture model

Abstract

Background Hypoxia contributes to retinal damage in several retinal diseases, including central retinal artery occlusion, with detrimental consequences like painless, monocular loss of vision. Currently, the treatment options are severely limited due to the short therapy window, as the neuronal cells, especially the retinal ganglion cells (RGCs), are irreversibly damaged within the first few hours. Hypothermia might be a possible treatment option or at least might increase the therapy window. Methods To investigate the neuroprotective effect of hypothermia after retinal hypoxia, an easy‐to‐use ex vivo retinal hypoxia organ culture model developed in our laboratory was used that reliably induced retinal damage on a structural, molecular and functional level. The neuroprotective effect of hypothermia after retinal hypoxia was analysed using optical coherence tomography scans, histological stainings, quantitative real‐time polymerase chain reaction, western blotting and microelectrode array recordings. Results Two different hypothermic temperatures (30°C and 20°C) were evaluated, both exhibited strong neuroprotective effects. Most importantly, hypothermia increased RGC survival after retinal hypoxia. Furthermore, hypothermia counteracted the hypoxia‐induced RGC death, reduced macroglia activation, attenuated retinal thinning and protected from loss of spontaneous RGC activity. Conclusions These results indicate that already a mild reduction in temperature protects the RGCs against damage and could function as a promising therapeutic option for hypoxic diseases.

Mouth breathing impairs the development of temporomandibular joint at a very early stage

“…Nasal obstruction and hypoxia are both stimuli for the growth and development of rats throughout the process. Moreover, prolonged hypoxia can cause significant pathological changes in organs such as the skull, eyes, kidney, cardiovascular system, and gastrointestinal tract (Damman, Bloks, & Daha, 2015; Jakus, Jakus, Aračić, Stipić, & Vilović, 2017; Kim, Fong, Pilowsky, & Abbott, 2018; Klemm, Hurst, & Dias Blak, 2019; Wang et al., 2013; Yuan et al., 2018). However, at the very early stage, hypoxia is not as significant in remodeling the condyles of rats as mouth breathing.…”

Novel Porcine Retina Cultivation Techniques Provide Improved Photoreceptor Preservation

“…During the whole procedure, attention was paid to keep constant aseptic conditions and to prevent a dehydration of the explant. The retina thickness was evaluated according to established protocols ( Schnichels et al, 2016 ; Klemm et al, 2019 ). To this end, the thickness was measured five times per picture via ImageJ (version 1.3u, National Institutes of Health, Bethesda, MD, United States).…”

Organ Cultures for Retinal Diseases

“…Thus, these ex vivo models are comparable to the in vivo situation where the outer retina is still nourished while the inner retina lacks oxygen, glucose, and other nutrients. These models were also used to test possible therapies as hypothermia, which represents an already established therapy in neurology (Schultheiss et al, 2016;Klemm et al, 2019). Hypothermia treatment on retinae under hypoxic stress prevented the death of RGCs and attenuated the gliosis response (Klemm et al, 2019).…”