Xenografts of islets of Langerhans in the vitreous cavity
Purpose. Intraocular spaces, including the anterior chamber, vitreous cavity, and subretinal space, are immunologically privileged sites. Unlike grafts into immunologically privileged sites such as brain or testis, the fate of tissue transplanted into the vitreous cavity may be directly observed in vivo. The purpose of this study was to determine if murine islets of Langerhans transplanted into the vitreous cavity of rabbits maintain their viability and fail to provoke an immune response. Methods. Islets from donor CD-1 mice were isolated by collagenase digestion and manual sorting. Five Dutch-belted rabbits received transplants of mouse islets into the vitreous cavity of one eye. Using a hyaluronidase solution, a pocket of liquified vitreous was created above the nasal retinal vascular wing, followed by preretinal injection of islets through a 27-gauge needle. The islet xenografts were observed by indirect ophthalmoscopy, color fundus photography, and flourescein angiography for 4 days (four rabbits) and 14 days (one rabbit). At sacrifice, the eyes were fixed for light microscopy. Results. No ophthalmoscopically visible inflammatory reaction was observed in the vitrous cavity at any time in any of the animals. The preretinal islets became less visible by the end of the observation period. In the 14-day animal, changes occurred in the orientation of the retinal blood vessels. However, the islets did not hyperfluoresce on angiography in any of the animals, suggesting that neovascularization had not yet occurred. Conclusions. Murine islet xenografts into the vitreous cavity of rabbits did not provoke a clinically visible inflammatory reaction and persisted for periods up to 14 days. Presence or absence of neovascularization will be determined histologically, and more animals will be evaluated for longer time periods. Transplantation of islets of Langerhans into an immune privileged site may provide an alternative to insulin injections for diabetic patients and reduce or eliminate the need for systemic immunosuppression.
Nelson, CP; Embabi, SN; Hatchell, DL
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