Recent advances in nonhuman primate models of macular diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

He Hailong ,  Jin Zibing

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing 100005, China;

Corresponding author：

Jin Zibing, Email: jinzb502@ccmu.edu.cn

Keywords：

Nonhuman primate; Animal model; Macular diseases; Review

DOI：

10.3760/cma.j.cn511434-20221207-00647

Video：

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The macula is a critical anatomical structure for primates to acquire high-resolution spatial and color vision, with macula lesions posing a significant threat to patients' visual function and quality of life. Non-human primate (NHP) are the only mammals with a macular structure that is closest to that of humans, thus offering substantial value in the study of macular diseases. Currently, various methods, including spontaneous occurrence, gene editing, drug-induced, light-induced, and mechanical injury, can be employed to screen and establish NHP models for investigating conditions such as oculocutaneous albinism, achromatopsia, retinitis pigmentosa, age-related macular degeneration, and certain rare ocular syndromes. When constructing NHP models, due consideration should be given to other animal models to facilitate complementary research across different model systems. Additionally, leveraging the advantages of NHP and establishing genetically controlled NHP strains is a goal to strive for to achieve sustainable utilization of these resources in research.

Citation： He Hailong, Jin Zibing. Recent advances in nonhuman primate models of macular diseases. Chinese Journal of Ocular Fundus Diseases, 2023, 39(11): 953-957. doi: 10.3760/cma.j.cn511434-20221207-00647 Copy

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2.	Shibuya K, Tomohiro M, Sasaki S, et al. Characteristics of structures and lesions of the eye in laboratory animals used in toxicity studies[J]. J Toxicol Pathol, 2015, 28(4): 181-188. DOI: 10.1293/tox.2015-0037.
3.	Warren WC, Harris RA, Haukness M, et al. Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility[J/OL]. Science, 2020, 370(6523): e6617[2020-12-18]. https://pubmed.ncbi.nlm.nih.gov/33335035/. DOI: 10.1126/science.abc6617.
4.	Francis PJ, Appukuttan B, Simmons E, et al. Rhesus monkeys and humans share common susceptibility genes for age-related macular disease[J]. Hum Mol Genet, 2008, 17(17): 2673-2680. DOI: 10.1093/hmg/ddn167.
5.	Wu KC, Lv JN, Yang H, et al. Nonhuman primate model of oculocutaneous albinism with TYR and OCA2 mutations[J/OL]. Research (Wash DC), 2020, 2020: 1658678[2020-03-11]. https://pubmed.ncbi.nlm.nih.gov/32259106/. DOI: 10.34133/2020/1658678.
6.	Moshiri A, Chen R, Kim S, et al. A nonhuman primate model of inherited retinal disease[J]. J Clin Invest, 2019, 129(2): 863-874. DOI: 10.1172/JCI123980.
7.	Uyhazi KE, Bennett J. Blinded by the light: a nonhuman primate model of achromatopsia[J]. J Clin Invest, 2019, 129(2): 513-515. DOI: 10.1172/JCI126205.
8.	Ikeda Y, Nishiguchi KM, Miya F, et al. Discovery of a cynomolgus monkey family with retinitis pigmentosa[J]. Invest Ophthalmol Vis Sci, 2018, 59(2): 826-830. DOI: 10.1167/iovs.17-22958.
9.	Peterson SM, McGill TJ, Puthussery T, et al. Bardet-Biedl syndrome in rhesus macaques: a nonhuman primate model of retinitis pigmentosa[J/OL]. Exp Eye Res, 2019, 189: 107825[2019-10-04]. https://pubmed.ncbi.nlm.nih.gov/31589838/. DOI: 10.1016/j.exer.2019.107825.
10.	Yiu G, Tieu E, Munevar C, et al. In vivo multimodal imaging of drusenoid lesions in rhesus macaques[J/OL]. Sci Rep, 2017, 7(1): 15013[2017-11-03]. https://pubmed.ncbi.nlm.nih.gov/29101353/. DOI: 10.1038/s41598-017-14715-z.
11.	Zeng B, Zhang H, Peng Y, et al. Spontaneous fundus lesions in elderly monkeys: an ideal model for age-related macular degeneration and high myopia clinical research[J/OL]. Life Sci, 2021, 282: 119811[2021-10-01]. https://pubmed.ncbi.nlm.nih.gov/34256039/. DOI: 10.1016/j.lfs.2021.119811.
12.	Gouras P, Ivert L, Landauer N, et al. Drusenoid maculopathy in rhesus monkeys (Macaca mulatta): effects of age and gender[J]. Graefe's Arch Clin Exp Ophthalmol, 2008, 246(10): 1395-1402. DOI: 10.1007/s00417-008-0910-8.
13.	Maloca PM, Freichel C, Hänsli C, et al. Cynomolgus monkey's choroid reference database derived from hybrid deep learning optical coherence tomography segmentation[J/OL]. Sci Rep, 2022, 12(1): 13276[2022-08-02]. https://pubmed.ncbi.nlm.nih.gov/35918392/. DOI: 10.1038/s41598-022-17699-7.
14.	Winkler PA, Occelli LM, Petersen-Jones SM. Large animal models of inherited retinal degenerations: a review[J]. Cells, 2020, 9(4): 882. DOI: 10.3390/cells9040882.
15.	Lin Q, Lv JN, Wu KC, et al. Generation of nonhuman primate model of cone dysfunction through in situ AAV-mediated CNGB3 ablation[J]. Mol Ther Methods Clin Dev, 2020, 18: 869-879. DOI: 10.1016/j.omtm.2020.08.007.
16.	Li S, Hu Y, Li Y, et al. Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina[J]. Sci Bull (Beijing), 2021, 66(4): 374-385. DOI: 10.1016/j.scib.2020.09.008.
17.	Ryu J, Statz JP, Chan W, et al. CRISPR/Cas9 editing of the MYO7A gene in rhesus macaque embryos to generate a primate model of usher syndrome type 1B[J/OL]. Sci Rep, 2022, 12(1): 10036[2022-06-16]. https://pubmed.ncbi.nlm.nih.gov/35710827/. DOI: 10.1038/s41598-022-13689-x.
18.	Teo KYC, Lee SY, Barathi AV, et al. Surgical removal of internal limiting membrane and layering of AAV vector on the retina under air enhances gene transfection in a nonhuman primate[J]. Invest Ophthalmol Vis Sci, 2018, 59(8): 3574-3583. DOI: 10.1167/iovs.18-24333.
19.	Gao G, He L, Liu S, et al. Establishment of a rapid lesion-controllable retinal degeneration monkey model for preclinical stem cell therapy[J/OL]. Cells, 2020, 9(11): 2468[2022-11-13]. https://pubmed.ncbi.nlm.nih.gov/33202702/. DOI: 10.3390/cells9112468.
20.	Shirai H, Mandai M, Matsushita K, et al. Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration[J/OL]. Proc Natl Acad Sci USA, 2016, 113(1): E81-90[2016-01-05]. https://pubmed.ncbi.nlm.nih.gov/26699487/. DOI: 10.1073/pnas.1512590113.
21.	Lingam S, Liu Z, Yang B, et al. cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates[J]. Stem Cell Res Ther, 2021, 12(1): 464. DOI: 10.1186/s13287-021-02539-8.
22.	Ou Q, Zhu T, Li P, et al. Establishment of retinal degeneration model in rat and monkey by intravitreal injection of sodium iodate[J]. Curr Mol Med, 2018, 18(6): 352-364. DOI: 10.2174/1566524018666181113104023.
23.	Tu HY, Watanabe T, Shirai H, et al. Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration[J]. EBioMedicine, 2019, 39: 562-574. DOI: 10.1016/j.ebiom.2018.11.028.
24.	Liu YV, Konar G, Aziz K, et al. Localized structural and functional deficits in a nonhuman primate model of outer retinal atrophy[J]. Invest Ophthalmol Vis Sci, 2021, 62(13): 8. DOI: 10.1167/iovs.62.13.8.
25.	Strazzeri JM, Hunter JJ, Masella BD, et al. Focal damage to macaque photoreceptors produces persistent visual loss[J]. Exp Eye Res, 2014, 119: 88-96. DOI: 10.1016/j.exer.2013.11.001.
26.	Dhakal KR, Walters S, McGregor JE, et al. Localized photoreceptor ablation using femtosecond pulses focused with adaptive optics[J]. Transl Vis Sci Technol, 2020, 9(7): 16. DOI: 10.1167/tvst.9.7.16.
27.	Rajagopalan L, Ghosn C, Tamhane M, et al. A nonhuman primate model of blue light-induced progressive outer retina degeneration showing brimonidine drug delivery system-mediated cyto- and neuroprotection[J/OL]. Exp Eye Res, 2021, 209: 108678[2019-06-19]. https://pubmed.ncbi.nlm.nih.gov/34153289/. DOI: 10.1016/j.exer.2021.108678.
28.	Cheong KX, Barathi VA, Teo KYC, et al. Choroidal and retinal changes after systemic adrenaline and photodynamic therapy in non-human primates[J]. Invest Ophthalmol Vis Sci, 2021, 62(3): 25. DOI: 10.1167/iovs.62.3.25.
29.	Fabian-Jessing BK, Jakobsen TS, Jensen EG, et al. Animal models of choroidal neovascularization: a systematic review[J]. Invest Ophthalmol Vis Sci, 2022, 63(9): 11. DOI: 10.1167/iovs.63.9.11.
30.	Lukason M, DuFresne E, Rubin H, et al. Inhibition of choroidal neovascularization in a nonhuman primate model by intravitreal administration of an AAV2 vector expressing a novel anti-VEGF molecule[J]. Mol Ther, 2011, 19(2): 260-265. DOI: 10.1038/mt.2010.230.
31.	Liu Z, Ilmarinen T, Tan GSW, et al. Submacular integration of hESC-RPE monolayer xenografts in a surgical non-human primate model[J]. Stem Cell Res Ther, 2021, 12(1): 423. DOI: 10.1186/s13287-021-02395-6.
32.	Seah I, Liu Z, Soo Lin Wong D, et al. Retinal pigment epithelium transplantation in a non-human primate model for degenerative retinal diseases[J/OL]. J Vis Exp, 2021, 1(172): E1[2021-06-14]. https://pubmed.ncbi.nlm.nih.gov/34180899/. DOI: 10.3791/62638.
33.	Thieltges F, Liu Z, Brinken R, et al. Localized RPE removal with a novel instrument aided by viscoelastics in rabbits[J]. Transl Vis Sci Technol, 2016, 5(3): 11. DOI: 10.1167/tvst.5.3.11.

1. Bringmann A, Syrbe S, Görner K, et al. The primate fovea: structure, function and development[J]. Prog Retin Eye Res, 2018, 66: 49-84. DOI: 10.1016/j.preteyeres.2018.03.006.
2. Shibuya K, Tomohiro M, Sasaki S, et al. Characteristics of structures and lesions of the eye in laboratory animals used in toxicity studies[J]. J Toxicol Pathol, 2015, 28(4): 181-188. DOI: 10.1293/tox.2015-0037.
3. Warren WC, Harris RA, Haukness M, et al. Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility[J/OL]. Science, 2020, 370(6523): e6617[2020-12-18]. https://pubmed.ncbi.nlm.nih.gov/33335035/. DOI: 10.1126/science.abc6617.
4. Francis PJ, Appukuttan B, Simmons E, et al. Rhesus monkeys and humans share common susceptibility genes for age-related macular disease[J]. Hum Mol Genet, 2008, 17(17): 2673-2680. DOI: 10.1093/hmg/ddn167.
5. Wu KC, Lv JN, Yang H, et al. Nonhuman primate model of oculocutaneous albinism with TYR and OCA2 mutations[J/OL]. Research (Wash DC), 2020, 2020: 1658678[2020-03-11]. https://pubmed.ncbi.nlm.nih.gov/32259106/. DOI: 10.34133/2020/1658678.
6. Moshiri A, Chen R, Kim S, et al. A nonhuman primate model of inherited retinal disease[J]. J Clin Invest, 2019, 129(2): 863-874. DOI: 10.1172/JCI123980.
7. Uyhazi KE, Bennett J. Blinded by the light: a nonhuman primate model of achromatopsia[J]. J Clin Invest, 2019, 129(2): 513-515. DOI: 10.1172/JCI126205.
8. Ikeda Y, Nishiguchi KM, Miya F, et al. Discovery of a cynomolgus monkey family with retinitis pigmentosa[J]. Invest Ophthalmol Vis Sci, 2018, 59(2): 826-830. DOI: 10.1167/iovs.17-22958.
9. Peterson SM, McGill TJ, Puthussery T, et al. Bardet-Biedl syndrome in rhesus macaques: a nonhuman primate model of retinitis pigmentosa[J/OL]. Exp Eye Res, 2019, 189: 107825[2019-10-04]. https://pubmed.ncbi.nlm.nih.gov/31589838/. DOI: 10.1016/j.exer.2019.107825.
10. Yiu G, Tieu E, Munevar C, et al. In vivo multimodal imaging of drusenoid lesions in rhesus macaques[J/OL]. Sci Rep, 2017, 7(1): 15013[2017-11-03]. https://pubmed.ncbi.nlm.nih.gov/29101353/. DOI: 10.1038/s41598-017-14715-z.
11. Zeng B, Zhang H, Peng Y, et al. Spontaneous fundus lesions in elderly monkeys: an ideal model for age-related macular degeneration and high myopia clinical research[J/OL]. Life Sci, 2021, 282: 119811[2021-10-01]. https://pubmed.ncbi.nlm.nih.gov/34256039/. DOI: 10.1016/j.lfs.2021.119811.
12. Gouras P, Ivert L, Landauer N, et al. Drusenoid maculopathy in rhesus monkeys (Macaca mulatta): effects of age and gender[J]. Graefe's Arch Clin Exp Ophthalmol, 2008, 246(10): 1395-1402. DOI: 10.1007/s00417-008-0910-8.
13. Maloca PM, Freichel C, Hänsli C, et al. Cynomolgus monkey's choroid reference database derived from hybrid deep learning optical coherence tomography segmentation[J/OL]. Sci Rep, 2022, 12(1): 13276[2022-08-02]. https://pubmed.ncbi.nlm.nih.gov/35918392/. DOI: 10.1038/s41598-022-17699-7.
14. Winkler PA, Occelli LM, Petersen-Jones SM. Large animal models of inherited retinal degenerations: a review[J]. Cells, 2020, 9(4): 882. DOI: 10.3390/cells9040882.
15. Lin Q, Lv JN, Wu KC, et al. Generation of nonhuman primate model of cone dysfunction through in situ AAV-mediated CNGB3 ablation[J]. Mol Ther Methods Clin Dev, 2020, 18: 869-879. DOI: 10.1016/j.omtm.2020.08.007.
16. Li S, Hu Y, Li Y, et al. Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina[J]. Sci Bull (Beijing), 2021, 66(4): 374-385. DOI: 10.1016/j.scib.2020.09.008.
17. Ryu J, Statz JP, Chan W, et al. CRISPR/Cas9 editing of the MYO7A gene in rhesus macaque embryos to generate a primate model of usher syndrome type 1B[J/OL]. Sci Rep, 2022, 12(1): 10036[2022-06-16]. https://pubmed.ncbi.nlm.nih.gov/35710827/. DOI: 10.1038/s41598-022-13689-x.
18. Teo KYC, Lee SY, Barathi AV, et al. Surgical removal of internal limiting membrane and layering of AAV vector on the retina under air enhances gene transfection in a nonhuman primate[J]. Invest Ophthalmol Vis Sci, 2018, 59(8): 3574-3583. DOI: 10.1167/iovs.18-24333.
19. Gao G, He L, Liu S, et al. Establishment of a rapid lesion-controllable retinal degeneration monkey model for preclinical stem cell therapy[J/OL]. Cells, 2020, 9(11): 2468[2022-11-13]. https://pubmed.ncbi.nlm.nih.gov/33202702/. DOI: 10.3390/cells9112468.
20. Shirai H, Mandai M, Matsushita K, et al. Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration[J/OL]. Proc Natl Acad Sci USA, 2016, 113(1): E81-90[2016-01-05]. https://pubmed.ncbi.nlm.nih.gov/26699487/. DOI: 10.1073/pnas.1512590113.
21. Lingam S, Liu Z, Yang B, et al. cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates[J]. Stem Cell Res Ther, 2021, 12(1): 464. DOI: 10.1186/s13287-021-02539-8.
22. Ou Q, Zhu T, Li P, et al. Establishment of retinal degeneration model in rat and monkey by intravitreal injection of sodium iodate[J]. Curr Mol Med, 2018, 18(6): 352-364. DOI: 10.2174/1566524018666181113104023.
23. Tu HY, Watanabe T, Shirai H, et al. Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration[J]. EBioMedicine, 2019, 39: 562-574. DOI: 10.1016/j.ebiom.2018.11.028.
24. Liu YV, Konar G, Aziz K, et al. Localized structural and functional deficits in a nonhuman primate model of outer retinal atrophy[J]. Invest Ophthalmol Vis Sci, 2021, 62(13): 8. DOI: 10.1167/iovs.62.13.8.
25. Strazzeri JM, Hunter JJ, Masella BD, et al. Focal damage to macaque photoreceptors produces persistent visual loss[J]. Exp Eye Res, 2014, 119: 88-96. DOI: 10.1016/j.exer.2013.11.001.
26. Dhakal KR, Walters S, McGregor JE, et al. Localized photoreceptor ablation using femtosecond pulses focused with adaptive optics[J]. Transl Vis Sci Technol, 2020, 9(7): 16. DOI: 10.1167/tvst.9.7.16.
27. Rajagopalan L, Ghosn C, Tamhane M, et al. A nonhuman primate model of blue light-induced progressive outer retina degeneration showing brimonidine drug delivery system-mediated cyto- and neuroprotection[J/OL]. Exp Eye Res, 2021, 209: 108678[2019-06-19]. https://pubmed.ncbi.nlm.nih.gov/34153289/. DOI: 10.1016/j.exer.2021.108678.
28. Cheong KX, Barathi VA, Teo KYC, et al. Choroidal and retinal changes after systemic adrenaline and photodynamic therapy in non-human primates[J]. Invest Ophthalmol Vis Sci, 2021, 62(3): 25. DOI: 10.1167/iovs.62.3.25.
29. Fabian-Jessing BK, Jakobsen TS, Jensen EG, et al. Animal models of choroidal neovascularization: a systematic review[J]. Invest Ophthalmol Vis Sci, 2022, 63(9): 11. DOI: 10.1167/iovs.63.9.11.
30. Lukason M, DuFresne E, Rubin H, et al. Inhibition of choroidal neovascularization in a nonhuman primate model by intravitreal administration of an AAV2 vector expressing a novel anti-VEGF molecule[J]. Mol Ther, 2011, 19(2): 260-265. DOI: 10.1038/mt.2010.230.
31. Liu Z, Ilmarinen T, Tan GSW, et al. Submacular integration of hESC-RPE monolayer xenografts in a surgical non-human primate model[J]. Stem Cell Res Ther, 2021, 12(1): 423. DOI: 10.1186/s13287-021-02395-6.
32. Seah I, Liu Z, Soo Lin Wong D, et al. Retinal pigment epithelium transplantation in a non-human primate model for degenerative retinal diseases[J/OL]. J Vis Exp, 2021, 1(172): E1[2021-06-14]. https://pubmed.ncbi.nlm.nih.gov/34180899/. DOI: 10.3791/62638.
33. Thieltges F, Liu Z, Brinken R, et al. Localized RPE removal with a novel instrument aided by viscoelastics in rabbits[J]. Transl Vis Sci Technol, 2016, 5(3): 11. DOI: 10.1167/tvst.5.3.11.

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Recent advances in nonhuman primate models of macular diseases

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