Abstract
Age-related Macular Degeneration (AMD) is an up-to-date untreatable chronic neurodegenerative eye disease of multifactorial origin, and the main causes of blindness in over 65 y.o. people. It is characterized by a slow progression and the presence of a multitude of factors, highlighting those related to diet, genetic heritage and environmental conditions, present throughout each of the stages of the illness. Current therapeutic approaches, mainly consisting on intraocular drug delivery, are only used for symptoms relief and/or to decelerate the progression of the disease. Furthermore, they are overly simplistic and ignore the complexity of the disease and the enormous differences in the symptomatology between patients. Due to the wide impact of the AMD and the up-to-date absence of clinical solutions, Due to the wide impact of the AMD and the up-to-date absence of clinical solutions, different treatment options have to be considered. Cell therapy is a very promising alternative to drug-based approaches for AMD treatment. Cells delivered to the affected tissue as a suspension have shown poor retention and low survival rate. A solution to these inconveniences has been the encapsulation of these cells on biomaterials, which contrive to their protection, gives them support, and favor their retention of the desired area. We offer a two-papers critical review of the available and under development AMD therapeutic approaches, from a biomaterials and biotechnological point of view. We highlight benefits and limitations and we forecast forthcoming alternatives based on novel biomaterials and biotechnology methods. In this second part we review the preclinical and clinical cell-replacement approaches aiming at the development of efficient AMD-therapies, the employed cell types, as well as the cell-encapsulation and cell-implant systems. We discuss their advantages and disadvantages and how they could improve the survival and integration of the implanted cells.
Highlights
Age-Related Macular DegenerationAge-Related Macular Degeneration (AMD) is a multifactorial degenerative eye disease, estimated to affect nearly 290 million people by 2040 (Wong et al, 2014)
Retina’s outer sheet, the Photoreceptors, lies over three non-neural layers: choroid, Bruch’s membrane (BrM) and retinal pigment epithelium (RPE), all of them strongly involved in the development of the Age-Related Macular DegenerationAge-Related Macular Degeneration (AMD) (Figure 1; Hoon et al, 2014; Wong et al, 2014)
Since RPE cells’ therapeutic effects are conditioned by the polarization of the implanted cells as well as by their spatial arrangement in a monolayer settled in the subretinal space, there is a great challenge for injections of suspended cells (Miyagishima et al, 2016, 2017)
Summary
Age-Related Macular Degeneration (AMD) is a multifactorial degenerative eye disease, estimated to affect nearly 290 million people by 2040 (Wong et al, 2014). A Phase II study in which human fetal neural retinal tissue and RPE were transplanted together in a group of AMD patients, showed promising results (Radtke et al, 2008; U.S National Library of Medicine, 2020o). The vision improvement observed in treated patients began 6 months after transplantation, the time predicted for the fetal cells to differentiate into mature photoreceptors Another phase I/II study used HuCNS-SC R (human central nervous system stem cells) injected subretinally in AMD patients (U.S National Library of Medicine, 2020r). PMMA scaffolds and transplanted into the sub-retinal space, biocompatible and non-toxic, retained RPE cells better during transplant, integrated cells expressed mature and immature markers hRPCs differentiated into photoreceptors and migrated to the outer nuclear layer of mice retina scaffold mouse film/scaffold mouse.
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