Limitation of anatomical integration between subretinal transplants and the host retina.
OBJECTIVE
In previous studies of subretinal transplantation in rabbits, the host photoreceptor layer seemed to prevent the bridging of neuronal fibers between the graft and the host retina. The current study was undertaken to determine whether the same phenomenon occurs in transplants to the subretinal space of the vascularized retina of rats. Bridging of fibers was examined in transplants to animals of different genetic backgrounds (normal versus dystrophic rats), of different ages, and after different survival times.


METHODS
Sprague-Dawley (SD) rat retinal tissue from embryonic day (E)18 was subretinally grafted to adult (60-day-old) normal SD rats, to RCS rats (32 and 73 days old), and to adult (60-day-old) transgenic P23H rats. After various survival times (28-183 days), transplanted retinas were processed for routine histology and immunocytochemistry. Antibodies against calbindin, neuronal nitric oxide synthase (NOS), and protein kinase C (PKC) were used to identify specific retinal cell types and their processes.


RESULTS
The shape and position of the immunoreactive cell bodies indicated that the expected neuronal populations were labeled within the grafts and in the host retina. Labeled neuronal processes were also observed. In each case, NOS-, calbindin-, and PKC-immunolabeled fibers formed bridges between the graft and the host tissues. However, regardless of the extent of host photoreceptor cell loss, the age of the recipient, or the genetic background, bridging fibers were observed only in areas where the host photoreceptor layer was discontinuous or completely missing.


CONCLUSIONS
The present study demonstrates that the host photoreceptor layer plays a role in limiting graft-host anatomical integration.
Zhang
Yiqin
Y
Wallenberg Retina Center, Department of Ophthalmology, Lund University, Klinikgatan 26, S-221 84 Lund, Sweden.
Arnér
Karin
K
Ehinger
Berndt
B
Perez
Maria-Thereza R
MT
D000818:Animals; D030801:Animals, Genetically Modified; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000032:analysis; D064026:Calbindins; D016332:Fetal Tissue Transplantation / Q000473:pathology*; D019084:Fluorescent Antibody Technique, Indirect; D006085:Graft Survival; D008856:Microscopy, Fluorescence; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism / Q000473:pathology* / Q000601:surgery / Q000637:transplantation*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D012243:Rhodopsin / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D014795:Visual Pathways / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D012243:Rhodopsin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D011493:Protein Kinase C