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Glenn Yiu, Jun Wang, Yumei Li, Kevin Choy, Sina Farsiu, Leon Huynh, Karolina Paulina Roszak, Ala Moshiri, Sara M Thomasy, Rui Chen; Rhesus macaques with soft drusen share susceptibility genes with age-related macular degeneration in humans.. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1493.
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© ARVO (1962-2015); The Authors (2016-present)
Nonhuman primates are the only mammals that possess a macula and exhibit soft drusen similar to those in human age-related macular degeneration (AMD). Here, we explored if aged rhesus macaques with soft drusen share similar susceptibility genes as human AMD.
We performed whole exome sequencing from 15 unrelated rhesus macaques from the California National Primate Research Center (CNPRC) with soft drusen identified on color fundus photography (CFP) and spectral domain-optical coherence tomography (SD-OCT), and compared with sequence data from a reference cohort of more than 1,800 rhesus macaques from various primate research centers. Variants falling within the exons of the orthologues of 34 candidate genes identified from genome wide association studies (GWAS) for human AMD were identified.
Bilateral soft drusen were identified in 15 rhesus macaques with clinical exam, CFP, and SD-OCT. The mean number of macular soft drusen per eye was 25 +/- 31, with no evidence of advanced AMD features such as choroidal neovascularization or geographic atrophy in any study animal. Among genes associated with human AMD, we identified 6 new variants within 4 genes including COL4A3, TGFBR1, ADAMTS9, and CFH that are associated with soft drusen in macaques. All 4 of these genes are expressed in the retinal pigment epithelium (RPE). Although none of these novel variants correspond to human orthologues associated with progression to advanced AMD in humans, such as the well-characterized CFH Y402H variant, one identified variant in CFH appears to correspond to a critical binding position for C3b. Some variants such as those in TGFBR1 and ADAMTS9 also appear to be associated with drusen size and number in this cohort of animals.
Rhesus macaques with soft drusen share some susceptibility genes as those in human AMD including CFH, but not variants associated with progression to advanced AMD, consistent with the absence of advanced AMD features in this nonhuman primate model.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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