July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Development of diabetic retinopathy and age-related macular degeneration in aged and metabolic dysregulated non-human primates
Author Affiliations & Notes
  • Kai Ming Zhang
    Ophthalmology, Kunming Biomed International, Kunming, Yunnan, China
  • Jin-Hua Zhu
    Ophthalmology, Kunming Biomed International, Kunming, Yunnan, China
  • Qiu-Yan Yang
    Ophthalmology, Kunming Biomed International, Kunming, Yunnan, China
  • Rui Lin
    Laboratory for Stem Cell & Retinal Regeneration / Institute of Stem Cell Research / Division of Ophthalmic Genetics / The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Qiang Lin
    Laboratory for Stem Cell & Retinal Regeneration / Institute of Stem Cell Research / Division of Ophthalmic Genetics / The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Guang-Hui Jin
    Laboratory for Stem Cell & Retinal Regeneration / Institute of Stem Cell Research / Division of Ophthalmic Genetics / The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Li-Chuan Yang
    Ophthalmology, Kunming Biomed International, Kunming, Yunnan, China
  • Kun-Chao Wu
    Laboratory for Stem Cell & Retinal Regeneration / Institute of Stem Cell Research / Division of Ophthalmic Genetics / The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Chang-Jun Zhang
    Laboratory for Stem Cell & Retinal Regeneration / Institute of Stem Cell Research / Division of Ophthalmic Genetics / The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Tony Wang
    Ophthalmology, Kunming Biomed International, Kunming, Yunnan, China
  • Rosario Perez
    Ophthalmology, Kunming Biomed International, Kunming, Yunnan, China
  • Shao-Dong Li
    Ophthalmology, Kunming Biomed International, Kunming, Yunnan, China
  • Bob Zhang
    Ophthalmology, Kunming Biomed International, Kunming, Yunnan, China
  • Zi-Bing Jin
    Laboratory for Stem Cell & Retinal Regeneration / Institute of Stem Cell Research / Division of Ophthalmic Genetics / The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Footnotes
    Commercial Relationships   Kai Ming Zhang, Kunming Biomed International (E); Jin-Hua Zhu, Kunming Biomed International (E); Qiu-Yan Yang, Kunming Biomed International (E); Rui Lin, None; Qiang Lin, None; Guang-Hui Jin, None; Li-Chuan Yang, Kunming Biomed International (E); Kun-Chao Wu, None; Chang-Jun Zhang, None; Tony Wang, Kunming Biomed International (E); Rosario Perez, Kunming Biomed International (E); Shao-Dong Li, Kunming Biomed International (E); Bob Zhang, Kunming Biomed International (E); Zi-Bing Jin, None
  • Footnotes
    Support  Zhejiang Provincial Natural Science Foundation of China (LD18H120001LD to JZB); Natinal Key R&D Program of China (2017YFA0105300 to JZB); Natural Science Foundation of China (81522014 to JZB)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6550. doi:
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      Kai Ming Zhang, Jin-Hua Zhu, Qiu-Yan Yang, Rui Lin, Qiang Lin, Guang-Hui Jin, Li-Chuan Yang, Kun-Chao Wu, Chang-Jun Zhang, Tony Wang, Rosario Perez, Shao-Dong Li, Bob Zhang, Zi-Bing Jin; Development of diabetic retinopathy and age-related macular degeneration in aged and metabolic dysregulated non-human primates. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6550.

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

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Abstract

Purpose : Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the leading causes of blindness and there are unmet medical needs for effective therapeutics. The non-human primate (NHP) is a potentially reliable translational animal model for novel drug discovery. Therefore, developing NHP models for DR, AMD and other eye diseases will provide translational value to facilitate drug discovery. We conduct this study to identify and characterize DR, AMD and other eye diseases phenotypes in a large cohort of aged and/or high-fat diet (HFD)-induced type 2 diabetic NHPs at Kunming Biomed International (KBI) to support new eye disease drug discovery with substantive translational value.

Methods :
KBI has over 3000 metabolic disease male cynomolgus induced by either HFD feeding or natural aging. Metabolic disease progression was monitored longitudinally by body weight, intravenous glucose tolerance test (IVGTT), blood pressure and clinical chemistry. Diabetic monkeys are identified based on fasting glucose level > 100mg/dL, glucose disposal rate < 1.3% and HbA1c >5%.
All monkeys were anesthetized with IM ketamine (5-10 mg/kg) and xylazine (0.5-1 mg/kg). Refractive error was assessed using auto refractors keratometer; axial length (AL) was measured using Lenstar Biometer; color fundus photograph, auto fluorescein and fluorescein angiograph (FA) was assessed using a fundus camera with FA; retina thickness, retinal edema was assessed using ocular coherence tomography (OCT). Intra ocular pressure (IOP) was measured using a TonoVET.

Results :
As a progress report, total of 573 monkeys have been screened. Early DR was found in 6% of eyes in diabetic monkeys. In aged NHPs, drusen (soft-, hard- and pseudo-drusen), geographic atrophy and wet-AMD was found in 3%, 0.4% and 0.4% of eyes, respectively. Optic neuropathy was found in 0.4% of eyes. IOP was higher than 21 mmHg in 38% of eyes. High myopia (spherical equivalent, SE≥-6.00D), with/out different phenotypes of retinopathy, was found in 27% of eyes.

Conclusions : Variety of eye diseases, DR and AMD in particular, existed in large cohort of diabetic and/or aged cynomolgus in KBI. These monkey eyes with different diseases that manifested with similar pathological characteristics with human patients will be valuable for research to characterize therapeutics and understand the mechanisms.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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