Abstract
Purpose :
Adipose-derived stem cells (ASCs) have shown a strong protective effect on retinal degeneration disease (RD) after being transplanted into the subretinal space in an animal model. Recently, several clinical trials have been conducted to treat RD with vitreous chamber transplantation of stem cells, including ASCs. However, the outcomes of the clinical trials were not satisfactory. Therefore, the effect of transplantation sites, including subretinal space and vitreous chamber, on the outcome of stem cell-based therapy for RD was investigated.
Methods :
rat ASCs (rASCs) were isolated and labeled them with green fluorescence protein. Autologous rASCs were grafted into the subretinal space or vitreous chamber in a rat RD model induced by sodium iodate. The electric response was recorded by ERG. The anatomic structure of the retina was observed in cryosections of rat eyes at posttransplantation weeks 1, 2 and 4. Neural retina apoptosis and epiretinal membrane (ERM)-like structure formation were investigated by immunostaining
Results :
The rASCs that grafted in the subretinal space protected the retina from the damage caused by SI, including a partial recovering of the electric response and a reduction in rosette formation. However, intravitreal transplantation of rASCs resulted in an extinguished electric response, although the rosette formation and apoptosis of neural retina were reduced. rASCs formed a membrane in the vitreous chamber, resulting in retina folding at the injection site. Müller cells, retinal pigment epithelial cells and microglial cells migrated from the retina to the rASC-formed membrane and subsequently formed an ERM-like structure. Furthermore, vitreous fluid promoted rASC migration, and rASC-conditioned medium enhanced Müller cell migration as indicated by in vitro studies.
Conclusions :
These data suggested that the subretinal space, rather than the vitreous chamber, is the optimal transplantation site for ASC-based therapy for RD and that a deliberate decision should be made before transplantation of stem cells into the vitreous chamber to treat RD in clinical trials.
This is a 2020 ARVO Annual Meeting abstract.