Development of a post-vitrectomy injection of N-methyl-N-nitrosourea as a localized retinal degeneration rabbit model

Abstract

Since genetic models for retinal degeneration (RD) in animals larger than rodents have not been firmly established to date, we sought in the present study to develop a new rabbit model of drug-induced RD. First, intravitreal injection of N-methyl-N-nitrosourea (MNU) without vitrectomy in rabbits was performed with different doses. One month after injection, morphological changes in the retinas were identified with ultra-wide-field color fundus photography (FP) and fundus autofluorescence (AF) imaging as well as spectral-domain optical coherence tomography (OCT). Notably, the degree of RD was not consistently correlated with MNU dose. Then, to check the effects of vitrectomy on MNU-induced RD, the intravitreal injection of MNU after vitrectomy in rabbits was also performed with different doses. In OCT, while there were no significant changes in the retinas for injections up to 0.1 mg (i.e., sham, 0.05 mg, and 0.1 mg), outer retinal atrophy and retinal atrophy of the whole layer were observed with MNU injections of 0.3 mg and 0.5 mg, respectively. With this outcome, 0.2 mg MNU was chosen to be injected into rabbit eyes (n=10) at two weeks after vitrectomy for further study. Six weeks after injection, morphological identification with FP, AF, OCT, and histology clearly showed localized outer RD - clearly bordered non-degenerated and degenerated outer retinal area - in all rabbits. We suggest our post-vitrectomy MNU-induced RD rabbit model could be used as an interim animal model for visual prosthetics before the transition to larger animal models.