Abstract
Background Glaucoma is a chronic neurodegenerative disease, characterized by progressive, permanent visual loss resulting from irreversible retinal ganglion cells (RGC) degeneration. Replacement of degenerated RGCs is a promising strategy to restore visual function. We previously demonstrated FGF2 induced differentiation of mouse embryonic stem cells (ESC) to RGC lineage, capable of retinal Ganglion Cell Layer (GCL) integration upon transplantation in mice. Here, we evaluated possible improvement of visual function by transplantation of ES cell derived neural progenitors in RGC depleted glaucoma mice models.
Methods ESC derived neural progenitors (ES-NP) was transplanted into NMDA (N-Methyl-D-Aspartate) injected, RGC-ablated mouse models and a pre-clinical glaucoma mouse model (DBA/2J) having sustained higher intra ocular pressure (IOP). Visual acuity and functional integration was evaluated by behavioural experiments and immunohistochemistry, respectively.
Results Transplantation of GFP expressing ES-NPs in NMDA injected RGC depleted mice, differentiated to RGC lineage and got integrated into GCL. An improvement in visual acuity was observed after two months of transplantation, when compared to the pre-transplantation values. Expression of c-Fos in the transplanted cells, upon light induction, further suggests functional integration into the host retinal circuitry. However, transplantation in DBA/2J mouse showed no significant improvement in visual functions, due to the cell death by inherent high IOP.
Conclusions We showed that, transplantation of ES-NPs into the retina of RGC-ablated mouse models could survive, differentiate to RGC lineage, and functionally integrate into GCL to improve visual function. However, for the survival of transplanted cells in glaucoma, strategies to control the IOP are warranted.
List of abbreviations
- RGCs
- Retinal Ganglion Cells
- ES cell
- Embryonic Stem Cells
- ES-NP
- Embryonic stem cell derived Neural Progenitors
- IOP
- Intra Ocular Pressure
- NMDA
- N-Methyl-D-Aspartate
- GCL
- Ganglion Cell Layer
- SCN
- Suprachiasmatic Nuclei
- LGN
- Lateral Geniculate Nuclei
- SC
- Superior Colliculus
- ERG
- Electro Retinogram
- VEP
- Visual Evoked Potential