Human anterior chamber angle development without cell death or macrophage involvement

Purpose: The iridocorneal angle in the mammalian eye including the trabecular meshwork (TM) develops from undifferentiated mesenchyme/ neural crest between the iris root and cornea. The precise mechanisms underlying anterior angle development are unclear, and the contribution of cell death and phagocytic resorption by macrophages in angle development is controversial. In this study, we examined the human anterior chamber angle during various stages of development for evidence of cell death and phagocytic resorption. Methods: Eyes from the human fetus (F) of 7, 8, 9, 10, 11, 13, 15, 18, 19, 21, 22, 23, and 27 weeks as well as eyes from 5- and 11-month-old children and donors 24, 48, and 67 years of age were obtained. Formalin-fixed and paraffin-embedded sections were examined by hematoxylin and eosin (H&E) staining. Immunohistochemistry was performed using polyclonal antibodies against CD68. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) labeling was also performed to evaluate cell death. Results: By light microscopy, the development of human angle structures appeared to progress as previously described. Histological evidence of cellular death or resorption by macrophages was not observed. Furthermore, the chamber angle tissues did not stain with CD68 at any stage of development. Few CD68 positive cells were observed in the iris stroma and the anterior ciliary body between fetal weeks 10 and 18 (F10w and F18w). TUNEL labeled nuclei were not detected in the anterior chamber angle in any fetal or infant eyes. By contrast, TUNEL positive nuclei in TM cells were observed in the examined adult donor specimens. Conclusions: The results suggest that at the time points examined, neither cell death nor phagocytic resorption with macrophages appear to play a role in the development of the human anterior chamber angle.