Retinal Pigment Epithelium Transplantation in a Non-human Primate Model for Degenerative Retinal Diseases. 2021

Ivan Seah, and Zengping Liu, and Daniel Soo Lin Wong, and Wendy Wong, and Graham E Holder, and Veluchamy Amutha Barathi, and Gopal Lingam, and Xinyi Su, and Boris V Stanzel
Department of Ophthalmology, National University Hospital, Singapore.

Retinal pigment epithelial (RPE) transplantation holds great promise for the treatment of inherited and acquired retinal degenerative diseases. These conditions include retinitis pigmentosa (RP) and advanced forms of age-related macular degeneration (AMD), such as geographic atrophy (GA). Together, these disorders represent a significant proportion of currently untreatable blindness globally. These unmet medical needs have generated heightened academic interest in developing methods of RPE replacement. Among the animal models commonly utilized for preclinical testing of therapeutics, the non-human primate (NHP) is the only animal model that has a macula. As it shares this anatomical similarity with the human eye, the NHP eye is an important and appropriate preclinical animal model for the development of advanced therapy medicinal products (ATMPs) such as RPE cell therapy. This manuscript describes a method for the submacular transplantation of an RPE monolayer, cultured on a polyethylene terephthalate (PET) cell carrier, underneath the macula onto a surgically created RPE wound in immunosuppressed NHPs. The fovea-the central avascular portion of the macula-is the site of the greatest mechanical weakness during the transplantation. Foveal trauma will occur if the initial subretinal fluid injection generates an excessive force on the retina. Hence, slow injection under perfluorocarbon liquid (PFCL) vitreous tamponade is recommended with a dual-bore subretinal injection cannula at low intraocular pressure (IOP) settings to create a retinal bleb. Pretreatment with an intravitreal plasminogen injection to release parafoveal RPE-photoreceptor adhesions is also advised. These combined strategies can reduce the likelihood of foveal tears when compared to conventional techniques. The NHP is a key animal model in the preclinical phase of RPE cell therapy development. This protocol addresses the technical challenges associated with the delivery of RPE cellular therapy in the NHP eye.

UI MeSH Term Description Entries
D008268 Macular Degeneration Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms. Maculopathy,Maculopathy, Age-Related,Age-Related Macular Degeneration,Age-Related Maculopathies,Age-Related Maculopathy,Macular Degeneration, Age-Related,Macular Dystrophy,Maculopathies, Age-Related,Age Related Macular Degeneration,Age Related Maculopathies,Age Related Maculopathy,Age-Related Macular Degenerations,Degeneration, Macular,Dystrophy, Macular,Macular Degeneration, Age Related,Macular Degenerations,Macular Dystrophies,Maculopathies,Maculopathy, Age Related
D011323 Primates An order of mammals consisting of more than 300 species that include LEMURS; LORISIDAE; TARSIERS; MONKEYS; and HOMINIDS. They are characterized by a relatively large brain when compared with other terrestrial mammals, forward-facing eyes, the presence of a CALCARINE SULCUS, and specialized MECHANORECEPTORS in the hands and feet which allow the perception of light touch. Primate
D012160 Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent. Ora Serrata
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D055213 Retinal Pigment Epithelium The single layer of pigment-containing epithelial cells in the RETINA, situated closely to the tips (outer segments) of the RETINAL PHOTORECEPTOR CELLS. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment. Epithelium, Retinal Pigment,Pigment Epithelium, Retinal
D057092 Geographic Atrophy A form of MACULAR DEGENERATION also known as dry macular degeneration marked by occurrence of a well-defined progressive lesion or atrophy in the central part of the RETINA called the MACULA LUTEA. It is distinguishable from WET MACULAR DEGENERATION in that the latter involves neovascular exudates. Dry Macular Degeneration,Atrophies, Geographic,Atrophy, Geographic,Degeneration, Dry Macular,Degenerations, Dry Macular,Dry Macular Degenerations,Geographic Atrophies,Macular Degeneration, Dry,Macular Degenerations, Dry

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