The primate model for understanding and restoring vision

Abstract

Retinal degenerative diseases caused by photoreceptor cell death are major causes of irreversible vision loss. As only primates have a macula, the nonhuman primate (NHP) models have a crucial role not only in revealing biological mechanisms underlying high-acuity vision but also in the development of therapies. Successful translation of basic research findings into clinical trials and, moreover, approval of the first therapies for blinding inherited and age-related retinal dystrophies has been reported in recent years. This article explores the value of the NHP models in understanding human vision and reviews their contribution to the development of innovative therapeutic strategies to save and restore vision.

Cell Atlas of the Human Fovea and Peripheral Retina

“…For example, among mammals, only primates have a fovea, the small central region responsible for high acuity vision as well as most chromatic vision -and the region selectively affected in macular degeneration, diabetic macular edema and hereditary maculopathies (7,8). As a first step toward addressing these issues, we recently used high throughput single cell RNA-seq (scRNA-seq) to generate a retinal cell atlas from cynomolgus macaque (Macaca fascicularis), a non-human primate that is closely related to humans and frequently used in preclinical ophthalmological studies (9)(10)(11). We separately profiled peripheral retina and the fovea ( Fig.1a).…”

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

“…Inherited forms of retinal degeneration (RD) encompass a genetically and clinically heterogeneous group of disorders estimated to cause vision impairment and loss in more than 5.5 million individuals worldwide [1,2], with 282 mapped and identified retinal degenerative disease genes documented in the RetNet human database [3]. Animal models, such as non-human primates [4], dogs [5], mice [6,7], zebrafish [8], and fruit flies [9], have been used to identify candidates for human retinal disease genes, to elucidate pathological mechanisms, and to serve as a resource for exploring therapeutic approaches. As potential therapies for retinal diseases are investigated, the need for animal models increases.…”

Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insights into Glaucoma Pathogenesis

“…To address this issue, we profiled cells dissociated from anterior segment tissues of 4 model species: the Rhesus macaque (M. mulatta, 5158 cells); the cynomolgus Macaque (M. fascicularis, 9155 cells); the common swine (S. scrofa, 6709 cells); and mouse (M. musculus, 5067 cells). These species are among the most commonly used for studies on glaucoma: rhesus and cynomolgus monkeys are frequently used for basic studies of primate visual physiology and preclinical tests, respectively (Picaud et al,2019); porcine anterior segments are used in aqueous outflow studies (Bachmann et al, 2006); and the broadest range of genetically modified lines is available in mice (Fernandes et al, 2015). We used a machine learning algorithm (XGBoost; Chen and Guestrin, 2016; see Methods) to find correspondences of cell types in the model species with those in humans.…”

“…Second, we used the human atlas as a foundation for assessing four animal models frequently used to study AH outflow pathways and glaucoma -Cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta), pig (Sus scrofa) and mouse (Mus musculus) (Bachmann et al, 2006;Fernandes et al, 2015;Picaud et al,2019). The utility of these models depends in large part on the extent to which their cell types and patterns of gene expression in them correspond to those in humans.…”