Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

Abstract

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments.

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

“…Therapeutic RPE replacement strategies are currently tested in usually small clinical trials (phase I) for AMD and in some types of RP (China: NCT02755428, NCT03944239, NCT03046407; United States of America: NCT01345006, NCT01344993, NCT02286089). These strategies include cell suspension injection, transplantation of autologous RPE sheets, and transplantation of RPE-scaffolds to the subretinal space [19]. In parallel, preclinical trials are ongoing in both animal models with smaller eyes, such as mice and rats, or larger eyes, such as rabbits, pigs, and primates.…”

“…The clinical trials for cell-based therapies are in its infancy, so the extent of efficiency is unknown in humans. The main focus of these therapies is on the safety of the patients [19]. It is clear that current cell delivery systems need to be further improved and standardized.…”

MERTK mutation update in inherited retinal diseases

“…Our work expands the mutation spectrum of MERTK in IRD which spans the entire coding and splice regions of the gene. It sets basis for therapeutic intervention aiming at gene augmentation (Ghazi et al., ; LaVail, et al., ) or cell therapy (Jones, Lu, Girman, & Wang, ) for this genetic group linked to mutations in a selectively RPE‐expressed gene. Mutations in MERTK are however associated with early onset retinal degeneration with rapid macular involvement urging for early diagnosis and intervention in strategies aiming at rescuing photoreceptors.…”

Suprachoroidal Adipose Tissue-Derived Mesenchymal Stem Cell Implantation in Patients with Dry-Type Age-Related Macular Degeneration and Stargardt's Macular Dystrophy: 6-Month Follow-Up Results of a Phase 2 Study

“…Compared with BMMSCs, ADMSCs have the advantages of easier harvest from donors, faster expansion, more protein secretion, and higher immunomodulatory capacity ( Jones et al, 2017;Ö ner, 2018).…”