Abstract
Purpose :
Irreversible photoreceptor loss in retinal diseases leads to blindness. Therefore, we aim to treat by replacement of clinically safe and functional photoreceptors. We have developed a laminin based differentiation method that generates transplantable competent photoreceptor progenitors from human embryonic stem cells and have shown that they could partially restore retina function in rodents. However, the presence of a macula in non-human primate (NHP) bears the closest resemblance to humans, making it the most physiologically relevant animal model. Our hypothesis is that our laminin based differentiated photoreceptor progenitors could improve the retina function in NHPs by recapitulating the transplantation outcome as evidenced in our previous rodent study.
Methods :
We have developed NHP model with laser induced injury in the retina that leads to targeted photoreceptor disruption. Sub-retinal transplantation using our laminin based differentiated photoreceptor progenitors was performed in the targeted laser injured sites of 4 NHPs. Multifocal electroretinogram (mfERG) analysis was performed to compare the functional visual response between the pre and post laser injured retinas. Biweekly mfERG and optical coherence tomography (OCT) analyses were also performed on the post cell transplanted NHPs for a period of 3 months.
Results :
In contrast to the pre- laser injured retinas, significant reduction in mfERG amplitudes together with OCT analyses showed targeted photoreceptor disruption 1 week after laser injury. After 4 weeks post cell transplantation, 3 out of 4 NHPs exhibited 40% improvement in mfERG response as compared to non-transplanted eyes. At 10 weeks, 2 out of 4 NHPs continued to show 40% mfERG response improvement. However, the improvement reduced to 10% in these 2 NHPs after 12 weeks. Based on the OCT analyses, the mfERG responses appeared to be dependent on the anatomical cell engrafted regions, suggesting that optimal cell engraftment size could be required to improve retina function in long term.
Conclusions :
The NHPs transplanted with laminin based differentiated photoreceptor progenitors exhibited short term retina function improvement which could be a result of functional cell engraftment size. This may constitute an important step towards the future use of human embryonic stem cell derived photoreceptor progenitors to treat vision loss.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.