Cellular migration into neural retina following implantation of melanin granules in the subretinal space

Background: In some retinal diseases and following transplantation of retinal pigment epithelium (RPE), melanin granules are liberated to the subretinal space. Our aim was to investigate the cellular response to implanted extracellular melanin. Methods: After pars plana vitrectomy, 17 albino rabbits received a suspension of melanin granules in the subretinal space. Postoperative examination included ophthalmoscopy, color fundus photography, histology using monoclonal antibodies identifying RPE cells (AE1/3), macrophages (RAM II), B-lymphocytes (CD20) and T-lymphocytes (CD45), and electron microscopy. The follow-up time was 2 weeks, 4 weeks and 6 months. Results: On fundus photographs, the layer of melanin showed focal attenuation with lighter areas at 6 months. Melanin granules were phagocytosed by RPE cells and macrophages at 2 weeks, as identified by monoclonal antibodies. In areas where an abundance of melanin was present, multilayers of macrophages were seen associated with considerable photoreceptor damage. Pigment-laden cells invaded the neural retina. The cellular infiltration of the retina was focal, and when it involved the outer nuclear layer the photoreceptor damage was severe. Electron microscopy demonstrated the presence of melanosomes intracellularly in Muller glia. The process of phagocytosis and removal of melanin granules from the subretinal space was slow and not completed at 6 months. Conclusion: Our experiments show that implantation of melanin granules in the subretinal space of albino rabbits may induce a considerable phagocytic cellular response featuring the host's RPE, macrophages and glial cells. The migration of pigment-laden cells into the neural retina was associated with focal photoreceptor damage.