Retinoblasts

Retinoblasts, commonly referred to in developmental biology as retinal progenitor cells (RPCs), are the multipotent cells that populate the developing retina. Arising from the neural tube–derived optic vesicle during embryogenesis, RPCs proliferate and give rise to all neuronal and glial cell types of the mature retina, including ganglion cells, amacrine cells, horizontal cells, bipolar cells, photoreceptors (rods and cones), and Müller glia. The process is temporally regulated; early RPCs predominantly produce retinal ganglion cells and cone photoreceptors, while later RPCs generate rods, other interneurons, and glia. Differentiation is guided by intrinsic transcription factors such as PAX6, OTX2, ATOH7, CRX, NRL, and by extrinsic signaling cues including Notch, Wnt, Shh, FGF, and IGF signaling.

RB1 gene encodes the retinoblastoma protein (pRB), a key regulator of the cell cycle. In RPCs, pRB restrains cell cycle progression by inhibiting E2F transcription factors, allowing orderly exit from the cell cycle and initiation of differentiation. Disruption of RB1 function impairs cell cycle control, promoting proliferation of RPCs and increasing the risk of tumorigenesis in the retina.

Retinoblastoma is the malignant tumor that most commonly arises when both RB1 alleles are inactivated in retinal cells. It can be hereditary (germline RB1 mutation with a second somatic hit) or non-heritable (two somatic hits). Patients typically present in childhood with leukocoria or strabismus; treatment depends on disease stage and includes enucleation, chemotherapy, and focal therapies. The study of retinoblasts also informs understanding of retinal development and neuro-oncology.

See also: retina development, retinal progenitor cells, RB1 gene, retinoblastoma.