The retinal pigment epithelium undergoes massive apoptosis during early differentiation and pigmentation of the optic cup

[摘要] Purpose: The aim of our work was tostudy apoptosis during the development of the retinal pigmentepithelium (RPE) in mice between embryonic day (E) 10.5 and E12.5 andto examine a possible link between apoptosis and pigmentation. Methods: We collected mouse embryos atE10.5, E11.5, and E12.5 and labeled apoptotic cells in 5-µm paraffinsections, using the terminal deoxynucleotidyl transferase dUTP nick endlabeling technique. We counted the total number of cells and the numberof apoptotic cells in the early developing RPE and calculated thepercentage of apoptosis at each stage. Results: In the C57BL/6J mouse, 17% ofthe RPE cells were apoptotic at E10.5 compared to 0.9% at E12.5. AtE11.5, three-quarters of the RPE cells began to pigment, and apoptoticcells were located mostly in the nonpigmented part. In contrast, in theBALB/c mouse (tyrosinase-deficient) and pJ mouse (carrying mutations inthe p gene) hypopigmented strains, the RPE containedsignificantly fewer apoptotic cells (7.5% and 10.1%, respectively) atE10.5 than controls. Subsequently at E11.5 and E12.5, the twohypopigmented strains displayed different apoptotic patterns; theBALB/c RPE had a similar percentage of apoptotic cells to controls(1.5% and 1.1%, respectively, for BALB/c versus 3.0% and 0.9%,respectively, for C57BL/6J), whereas the pJ RPE contained significantlymore apoptosis (7.5% and 3.5%, respectively). Overall we observeddifferences in the evolution of the relative total number of RPE cellsbetween the three strains. Conclusions: Apoptosis is a main eventduring the first stages of normal RPE development, indicating anessential role during RPE differentiation. Moreover, the earlyapoptotic pattern and possibly the whole early development of the RPEis different between hypopigmented and pigmented strains, as well asbetween BALB/c and pJ mice. This suggests the existence of regulatoryand developmental differences with a more complex origin than justdiffering pigmentation levels.

[学科分类] 生物化学/生物物理