Effect of cyclosporine on anterior chamber-associated immune deviation with retinal transplantation.
OBJECTIVE
To determine whether immunosuppression using cyclosporine interferes with anterior chamber associated immune deviation (ACAID) and can promote survival of retinal allografts in the anterior chamber.


METHODS
Neonatal neural retinas of C57BL/6 mice or ovalbumin were injected into the anterior chamber of BALB/c adult mice. In the test group recipients were injected with cyclosporine (10 mg/kg per day) from day 0 to 11 or from day 11 to 34 after implantation. At 12 and 35 days after transplantation, lymphocytes from the test group were injected into naive BALB/c mice to assay for the presence of suppressor T cells (adoptive transfer). The fate of the retinal grafts was determined by histologic examination at day 12 and 35. To evaluate the potential neurotoxic effects of cyclosporine in the absence of immune rejection mechanisms, cyclosporine was given to SCID mice during days 11 to 34 after syngeneic neonatal neural retinal grafts were placed in the anterior chamber.


RESULTS
At 12 days after transplantation, spleens of both cyclosporine-treated and control mice contained suppressor cells against donor alloantigens. The retinal grafts in the anterior chamber of both groups of mice were fully developed and well differentiated. The same duration of administration of cyclosporine did not interfere with the production of efferent suppressor cells after inoculation of ovalbumin into the anterior chamber. At 35 days after transplantation, only spleen cells from the cyclosporine-treated group showed the capacity to suppress donor-specific delayed hypersensitivity. However, allografts in the cyclosporine group had deteriorated by 35 days in a fashion similar to the control group. Syngeneic grafts in SCID mice showed differentiated retinal layers 35 days after transplantation.


CONCLUSIONS
Cyclosporine treatment does not interfere with the ability of allogeneic neonatal retinal grafts to induce anterior chamber associated immune deviation when placed in the anterior chamber, nor does prolonged treatment with this drug interfere with the persistence of allospecific suppressor cells for 35 days after the graft. Because 35-day grafts of cyclosporine-treated mice display histologic evidence of graft failure similar to grafts placed in the anterior chamber of untreated mice, graft destruction is either the result of immune effector mechanisms not inhibited by cyclosporine, or the consequence of nonimmunologic factors.
Ishioka
M
M
Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.
Okamoto
S
S
Streilein
J W
JW
Jiang
L Q
LQ
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D000867:Anterior Chamber / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D012160:Retina / Q000473:pathology / Q000637:transplantation*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine