Iris movement mediates vascular apoptosis during rat pupillary membrane regression

Abstract

In the course of mammalian lens development, a transient capillary meshwork known as the pupillary membrane (PM) forms, which is located at the pupil area; the PM nourishes the anterior surface of the lens and then regresses to make the optical path clear. Although the involvement of apoptotic process has been reported in the PM regression, the initiating factor remains unknown. We initially found that regression of the PM coincided with the development of iris motility, and iris movement caused cessation and resumption of blood flow within the PM. Therefore, we investigated whether the development of the iris's ability to constrict and dilate functions as an essential signal that induces apoptosis in the PM. Continuous inhibition of iris movement with mydriatic agents from postnatal day 7 to day 12 suppressed apoptosis of the PM and migration of macrophage toward the PM, and resulted in the persistence of PM in rats. The distribution of apoptotic cells in the regressing PM was diffuse and showed no apparent localization. These results indicated that iris movement induced regression of the PM by changing the blood flow within it. This study suggests the importance of the physiological interactions between tissues-in this case, the iris and the PM-as a signal to advance vascular regression during organ development, and defines a novel function of the iris during ocular development in addition to the well-known function, that is, optimization of light transmission into the eye.

Ocular Phenotype ofFbn2-Null Mice

“…54 Alternatively, it has been proposed that regression is triggered when the iris gains the ability to contract and, in so doing, influences blood flow in the underlying PM vessels. 55 The latter explanation may be most consistent with the current findings where regression did not occur in the absence of overlying iridal tissue.…”

Dll4 Suppresses Transcytosis for Arterial Blood-Retinal Barrier Homeostasis

“…These data show that absence of macrophages leads to protrusion between looping vessels, where they failed to draw irises aside. To assess the blood flow known to be important for the regression of PM vessels (Morizane et al 2006;Meeson et al 1996), we applied in vivo imaging of VEGFR2-BAC-EGFP mice (Ishitobi et al, 2010). The result showed blood flow was abundant in looping vessels, but far less in the central vessels at P3, suggesting the programmed regression of PM vessels initially occurred in the central vessels in the later stages ( Fig.…”

Macrophages engulf endothelial cell membrane particles preceding pupillary membrane capillary regression

“…In keeping with this model, previous studies have indicated that rat PM regression is initiated by constriction and dilation of the iris preceding macrophage activation (Morizane et al, 2006). By treating the rat eye with mydriatics to prevent iris movement, it was found that PM vessels persisted and the number of apoptotic cells was reduced.…”

“…These data suggested that repeated constriction and dilation of the iris causes repetitive periods of bending and relaxation of the PM vessels at the iris margin. This, in turn, was thought to cause constant cessation and resumption of blood flow that ultimately induces vascular apoptosis (Morizane et al, 2006). Indeed, previous vital imaging studies of the rat PM also implicated flow stasis as a trigger for apoptosis observed in discrete vessel segments during later stages of regression (Meeson et al, 1996).…”