Weiming Yan,1,* Qiurui He,2,* Pan Long,3,* Lei Zhang,4 Haiyan Wang,4 Tao Chen5 

1Department of Ophthalmology, Fuzong Clinical Medical College of Fujian Medical University, Dongfang Hospital Affiliated to Xiamen University, Fuzhou, People’s Republic of China; 2Department of Cardiovascular Intervention, The Third Hospital of Zhangzhou, Zhangzhou, People’s Republic of China; 3Department of Ophthalmology, The General Hospital of Western Theatre Command, PLA, Chengdu, People’s Republic of China; 4Department of Ophthalmology, The Shaanxi Eye Hospital, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, People’s Republic of China; 5Center of Clinical Aerospace Medicine, Air Force Military Medical University, Xi’an, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Weiming Yan; Tao Chen, Email ywming@fjmu.edu.cn; baiidtf0506@126.com

Objective: With the aids of ophthalmic imaging techniques for animals, the spatiotemporal characterization of MNU-induced retinitis pigmentosa (RP) rats were performed.
Methods: Sprague-Dawley (SD) rats were randomly divided into normal group (N), MNU-low-dose group (L) and MNU-high-dose group (H). Rats in the L and H group were given intraperitoneally injection with 40 and 60 mg/kg of MNU, a kind of alkylating agent, respectively. The body weight, electroretinogram (ERG) and retinal structure were observed on day one (D1), D3, and D7 after MNU administration. FFA, OCT, TUNEL staining, and immunostaining of Iba1 were also performed.
Results: After MNU injection, the weight and ERG amplitudes of rats in both L and H groups decreased gradually, compared to those of the normal group (P < 0.05). Fundus imaging revealed enlargement of the optical disc and slightly reduced shadow of retinal vessels in both L and H groups, which were more obvious on D7. No significant morphological changes of retinal vessels were found under FFA. OCT and retinal histological examination revealed that outer nuclear layers (ONL) became thinner gradually in both L and H groups, and disappeared in H group at D7. MNU administration increased the numbers of apoptotic cells and Iba1-positive cells in the retinas gradually, showing a dose-dependent effect.
Conclusion: MNU gradually reduced the ONL thickness and the ERG amplitudes in the MNU-induced RP model revealed by various ophthalmic imaging techniques, along with the increased apoptosis of photoreceptors, the microglia cells activation, which provide indicators for new intervention effect for RP.

Keywords: retinitis pigmentosa, animal model, N-methyl-N-nitrosourea, microglia