gms | German Medical Science

Objective: Several eye diseases, e.g., diabetic retinopathy or glaucoma, are associated with retinal hypoxia. This lack of oxygen causes cell damage up to cell degeneration, ultimately leading to blindness. Especially retinal ganglion cells (RGCs) react very sensitive to hypoxia. Thus, to examine the electrical activity of RGCs and to analyze the effect of neuroprotective substances under hypoxic conditions is of great ophthalmologic interest.

Materials and methods: Using multielectrode array (MEA) recordings, two ex-vivo models were established to analyze the electrical activity of murine wild-type (wt) retina under hypoxic stress conditions. Hypoxia was induced by either stopping the perfusion with oxygen saturated medium or by exchanging it by nitrogen saturated medium. To analyze the influence of neuroprotective agents on the firing behavior of RGCs under hypoxic conditions, 2-aminoethanesulfonic acid (taurine) was added during a hypoxic period of 30 min.

Results: In both models, the electrical activity vanished during hypoxia. However, it conditionally returned after reestablishment of the conventional test conditions. With increasing duration of hypoxia, the number of recording channels decreased, on which activity could be redetected. After a hypoxic period of 30 min and a subsequent recovery time of 30 min, 59.4 ± 11.4% of the initially active channels showed a restored activity within the nitrogen model. Taurine had a positive influence on the electrical excitability of RGCs. A gene expression analysis showed no significant differences in between the ex-vivo test groups, but revealed an upregulation of pathways involved in cellular responses to stress compared to the in-vivo status.

Discussion: The ex-vivo models established here allow for the analysis of electrical RGC activity before, during and after hypoxic conditions as well as the testing of protective substances. Moreover, this MEA-based analysis can be adapted to mimic other retinal stress conditions.