Selective transcription factor induction in retinal pigment epithelial cells during photoreceptor phagocytosis

Expression of early response genes during rod outer segment phagocytosis by normal Long Evans and Royal College of Surgeons-rdy(+)p(+) rats and by dystrophic Royal College of Surgeons-p(+) rat retinal pigment epithelial cells was studied in primary cell culture. Northern analysis revealed that the abundance of zif-268 (egr-1), c-fos, and tis-1 (NGF1-B) mRNA was rapidly and transiently increased in normal retinal pigment epithelial cells during rod outer segment phagocytosis but not during phagocytosis of latex particles. No increase in gene expression was found in Royal College of Surgeons-p(+) dystrophic retinal pigment epithelial cells challenged with rod outer segments. As shown by electrophoretic mobility shift assay, a prominent short term increase in the intensity of the gel-shifted band was detected using nuclear protein extracts derived from rod outer segment-challenged, control retinal pigment epithelial cells and zif-268, AP-1, AP-2, or tis-1 consensus oligonucleotides. No such increase was detected when using nuclear factor KB consensus oligonucleotide or when the early response gene prostaglandin H synthase-2 mRNA was measured over the time course studied. The results suggest that in retinal pigment epithelial cells, rad outer segment-specific phagocytosis is accompanied by the selective expression of early response genes coding for transcription factors. The specific pattern of the induction of these transcription factors is predicted to modulate the expression of gene cascades.