Abstract
Purpose: :
To investigate the circuitry in long-term retinal progenitor sheet transplants to rats with retinal degeneration.
Methods: :
Five S334ter line 3 rats received retinal sheet transplants with or without growth factors (BDNF or GDNF) at the age of 24-40 days. Eyes were studied at 200 - 265 days after surgery. Tissues were processed according to the method of Jones et al. 2003 (Comp. Neurol. 464:1-16). Vibratome slices (100 µm) through the transplant zone were embedded in Eponate, sectioned into serial ultrathin datasets and probed for aspartate, glutamate, glycine, gluthathione, glutamine, arginine, taurine, GABA, rhodopsin, cone opsin, CRALBP, and DAPI.
Results: :
The transplant slices exhibited large areas of well-oriented photoreceptors (rods and cones) in contact with the host RPE. The most dramatic feature of the transplant was the extensive loss of retinal neurons, specifically bipolar cells. There was an inverse relationship between the thickness of the transplant photoreceptor layer and its inner plexiform layer in every sample, suggesting that the transplant maintains a constant thickness. Mixing of neuropil between host and transplant in regions was where the Müller cell seal between the host and transplant was interrupted.
Conclusions: :
The data suggest that any major communication between host and transplant is likely to involve amacrine cells, both glycinergic and GABAergic. Chains of amacrine cells could do an excellent job of generating alternative signal pathways between a transplant and a degenerating host retina.
Keywords: retinal connections, networks, circuitry • retinal degenerations: cell biology • transplantation