June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Development of a monkey model for evaluation of novel ocular drugs with long-term effect on retinal atrophy and vascular leakage/regeneration
Author Affiliations & Notes
  • Hui Zhang
    TriApex, Nanjing, Jiangsu, China
  • Jinhua Zhu
    Ophthalmology, Kunming Biomed International (KBI), Kunming, YunNan , China
  • Guanzhong Wang
    Ophthalmology, Kunming Biomed International (KBI), Kunming, YunNan , China
  • XiaoYing Liang
    Ophthalmology, Kunming Biomed International (KBI), Kunming, YunNan , China
  • ChunLei Ji
    TriApex, Nanjing, Jiangsu, China
  • Yan Liu
    Ophthalmology, Kunming Biomed International (KBI), Kunming, YunNan , China
  • Chen Xu
    Ophthalmology, Kunming Biomed International (KBI), Kunming, YunNan , China
  • TianYu Dong
    TriApex, Nanjing, Jiangsu, China
  • Lichuan Yang
    Ophthalmology, Kunming Biomed International (KBI), Kunming, YunNan , China
  • Footnotes
    Commercial Relationships   Hui Zhang TriApex, Code E (Employment); Jinhua Zhu Kunming Biomed International (KBI), Code E (Employment); Guanzhong Wang Kunming Biomed International (KBI), Code E (Employment); XiaoYing Liang Kunming Biomed International (KBI), Code E (Employment); ChunLei Ji TriApex, Code E (Employment); Yan Liu Kunming Biomed International (KBI), Code E (Employment); Chen Xu Kunming Biomed International (KBI), Code E (Employment); TianYu Dong TriApex, Code E (Employment); Lichuan Yang Kunming Biomed International (KBI), Code E (Employment)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2721. doi:
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      Hui Zhang, Jinhua Zhu, Guanzhong Wang, XiaoYing Liang, ChunLei Ji, Yan Liu, Chen Xu, TianYu Dong, Lichuan Yang; Development of a monkey model for evaluation of novel ocular drugs with long-term effect on retinal atrophy and vascular leakage/regeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2721.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : In this study, we would develop a DL-AAA monkey model that is able to test novel ocular drugs with long-term effect on vascular leakage/regeneration and retinal lesions. All of the lesions should be measured with clinically non-invasive imaging tools as that in patients.

Methods : 22 healthy older monkeys (20 y in average) were intravitreously administrated with one or two doses of DL-AAA (25 mg/ml or 50 mg/ml) at the dose level of 2.5/3.0/3.5/3.75/5mg. The right eye was administrated DL-AAA and the left eye was used as the control, except for 2 animals which had both eyes administrated DL-AAA. The fundus was examined and imaged by using colorful fundus photography, OCT, OCTA and FA, before dosing as the baseline and after dosing to follow the progressions of fundus changes. The longest follow-up period was currently over 80 weeks. Several eyes were further treated with market anti-VEGF drugs or a novel anti-VEGF molecule.

Results : 1). Persistent retinal vascular leakage was detected in about 50% of the eyes. The leakage often located in the area around the macula and the optic disk. It could maintain for multiple weeks (up to 80 weeks so far). 2). Cystoid Retinal edema was observed in all of eyes in variable degrees. It was particularly evident in the middle layers of the retina, often involving a large area, from the macular area to peripheral retina. The type of edematous change developed within 1-3 weeks after injection and was persistently present. 3). Retinal thinning occurred over time. The retinal atrophy could be seen in some layers or whole retina. 4). The size/shape of foveal avascular zone became smaller, often accompanied with increase of vascular density. 5). Anti-VEGF-drugs could markedly inhibit vascular leakage for 6-8w, while a novel drug molecule with longer term efficacy showed the inhibition over 50 weeks.

Conclusions : In this aged Cynomolgus monkeys DL-AAA induced vascular leakage, size/shape change in the foveal avascular zone, and macular/retinal cystoid edema as well as retinal atrophy were persistent for long term and could be measured by using non-invasive clinical imaging tools. This model is useful for evaluation of novel drug molecules designed for long term treatment of retinal edematous lesion and vascular leakage/regeneration. It may also use for studying new drugs with different targets/mechanisms.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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