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Human embryonic retinal cell transplants in athymic immunodeficient rat hosts
1Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, KY 40292.
Cell Transplantation
|November 1, 1994
Summary
Athymic nude rats successfully host human embryonic retinal cell transplants without immunosuppression, showing excellent long-term survival and development. This model offers consistent results and superior outcomes compared to immunosuppressed rats for retinal xenograft studies.
Area of Science:
- Ophthalmology
- Immunology
- Regenerative Medicine
Background:
- Human embryonic retinal cell transplantation is a potential therapy for retinal diseases.
- Immunosuppression is typically required for xenotransplantation, posing risks and complications.
- Athymic nude rats offer a potential alternative host model without immunosuppression.
Purpose of the Study:
- To evaluate the athymic nude rat as a host for human embryonic retinal cell transplantation without immunosuppression.
- To assess the long-term survival, development, and integration of these xenografts.
- To compare outcomes with previous studies using immunosuppressed rats.
Main Methods:
- Human embryonic retinal cells (9-13 weeks postconception) were transplanted into 28 athymic rats.
- Rats were monitored for up to 48 weeks post-surgery.
- Histology, immunohistochemistry (using markers like rhodopsin, S-antigen, NSE, SYN, opsins, vimentin, CRALBP, GFAP, MHC-II, Ox-42), and electron microscopy were used for analysis.
Main Results:
- Transplants from younger donors (9-11 weeks) showed robust growth (2-3 mm) with rosettes in 31/35 eyes.
- Transplants from older donors (12-13 weeks) had poorer survival (8/11 eyes), smaller size, and less organization.
- All transplants integrated well with host retinas, exhibiting healthy development with photoreceptors, rods, cones, and plexiform layers, even after long survival.
- Minimal signs of host immune response were observed, with occasional MHC-II positive macrophages.
Conclusions:
- Athymic nude rats provide an excellent, well-tolerated host model for human retinal xenografts, eliminating the need for immunosuppression.
- This model yields consistent results and superior long-term survival for both hosts and transplants compared to immunosuppressed models.
- The study demonstrates the feasibility of successful human retinal xenotransplantation in an immunocompetent host for future therapeutic applications.