Article
Establishment and characterization of a UV-induced photoreceptor degeneration mouse model
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Published: | November 30, 2017 |
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Objective: In order to test retinal implants and establish surgical procedures for patients suffering from retinal degenerative diseases, e.g. retinitis pigmentosa (RP), large-eye animal models emulating the characteristics of RP are required. Here, we characterize a unilateral UV-induced photoreceptor degeneration model in the mouse, which is required to transfer the method to the large-eye rabbit model.
Material and Methods: Left eyes of female C57Bl/6J mice (PNW 8-12) were irradiated with a UV-LED at 370 nm (7.5 J/cm²). A lens was placed between LED and cornea that allows illumination of about one third of the retina. At different times post irradiation (n=8 per group), optical coherence tomography (OCT) and full-field electroretinography (ERG) were performed. Finally, animals were euthanized and the eyes were used for immunohistochemistry (n=4 per group) or microelectrode array (MEA) recordings (n=4 per group). Right eyes served as non-treated controls.
Results: In OCT scans, a decreased thickness was visible at five days post irradiation (76 ± 2.9%), dropping to 60 ± 4.0% at one week and stabilizing at 50 ± 3.7% at two weeks after irradiation. In ERGs, the a-wave decreased to 34 ± 6.3%, while the b-wave dropped to 24.5 ± 8.9% at five days post irradiation without any recovery. In MEA recordings, oscillatory potentials with a mean frequency of 5.3 ± 0.7 Hz were detected, which occurred already five days after irradiation. Structural changes in the retina were observed in immunohistochemistry and were comparable to those known from rd10 mice. UV-irradiation is a suitable and efficient method to induce photoreceptor degeneration in the mouse retina, while leaving the other retinal layers intact. The restriction that only a third of the retina could be irradiated was compensated by the feasibility to identify and localize the degenerated area in OCT scans. The approach is currently transferred to the large-eye rabbit model, which will allow for testing and optimization of newly developed retinal devices.
Acknowledgement: DFG grants WA-1472/6-3 to PW, JO-1263/1-3 to SJ, and MU-3036/3-3 to FM.