gms | German Medical Science

In patients suffering from retinal degenerative diseases, e.g. retinitis pigmentosa, functionality can be regained by prostheses, where microelectrodes initiate the electrical stimulation of surviving retinal cells. To test newly developed retinal implants, a large-eye animal model is required that mimics the properties of this type of retinal degeneration. The unilateral induction of photoreceptor degeneration was induced by n-methyl-n-nitrosourea (MNU), using the contralateral eye as control. Initial experiments were carried out in C57BL/6J mice and the results were transferred to the chinchilla bastard rabbit model. Firstly, the concentration of the intravitreal MNU injection was calculated depending on the bodyweight. In a second step, the MNU concentration was adjusted to the vitreous volumes of the respective rabbit eyes, calculated using ultrasound biometry. After injection, a weekly follow-up using optical coherence tomography (OCT) and electroretinogram (ERG) was performed. Rabbits were additionally examined using funduscopy and macroscopy. Mice and rabbits were sacrificed after two and three weeks, respectively, and the eyes were prepared for immunohistochemistry. In MNU-injected mice, the ERG became extinguished, OCT scans revealed a thinning of the retina, and immunohistochemical stainings demonstrated the selective loss of rods and cones. In rabbits, MNU-treated eyes revealed scattered areas of photoreceptor degeneration. Additionally, various side effects on the retina itself, e.g. retinal detachment and retinal tears, as well as on other ocular tissues, e.g. chemosis and lens lesions, were observed. However, in both species, the contralateral eye was not affected. Intravitreal injections of MNU induced a reliable photoreceptor degeneration in mice. However, in rabbits, the experiments were impeded by several difficulties. The poor solubility of MNU at higher concentrations affected the injected dosage in an uncontrollable manner. In addition, it is not exactly known, how MNU interacts with the vitreous body, thus possibly interfering with the consistent dispersion of MNU.

Acknowledgements: This work was supported by DFG grant DFG WA 1472/6-1, DFG PAK 469.