Retinal proliferation in response to vitreous hemoglobin or iron

To examine the effects of blood components within the vitreous on proliferation by cells in the retina, homologous hemoglobin or FeSO4 was injected into the rabbit vitreous. Cells undergoing DNA synthesis were labeled by 3H-thymidine injected into the vitreous or into the circulation. Both hemoglobin and FeSO4 stimulate proliferation in cells throughout the retina. There are two periods of increased retinal labeling. The first occurs 3 to 4 days after first contact with the introduced agents, and the second occurs after 2 to 4 weeks. Analysis of movement of cells after hemoglobin injection suggests that many labeled cells seen in the retina in the early period of labeling migrate from the outer layers toward the vitreous. Other data indicate that many of these cells are of hematogenous origin. Labeled cells also enter the vitreous from the region of the ciliary processes at this time. During the second period of retinal labeling, many proliferating cells may pass in the opposite direction through the retina toward the choroid. The accumulated data imply that the rabbit retina does not act as barrier to transmigrating cells after vitreous injury. Intravitreal hemoglobin also promotes cell multiplication in cells of the pigmented epithelium and possibly in some populations of retinal glial cells. Since these cells have been identified within the vitreous in some pathologic conditions, their suggested ability to respond by proliferation to a hemoglobin stimulus implies that vitreous hemorrhage may aggravate these pathologies in part by promoting multiplication of invasive cells.