Artificial extrauterine environment supports retinal development in preterm fetal lambs

Abstract

Purpose : The creation of an artificial extrauterine environment able to support normal somatic growth has fundamental implications for the physiologic support of premature infants. EXTrauterine Environment for Neonatal Development (EXTEND) is a pumpless extracorporeal system that has been shown in a landmark study to support the development of extreme preterm fetal lambs for up to 4 weeks (Partridge et al. 2017). However, the effect of the artificial womb on the maturation of the retina is unknown. We performed a histologic analysis to determine if EXTEND promotes normal retinal development.

Methods : Twelve eyes of six lambs were examined. Six eyes were from control fetal lambs delivered via C-section at 108, 131, and 135 days after conception (full term 145 days). Six eyes were from lambs delivered via C-section and subsequently supported on EXTEND for 20, 29, and 27 days. Lambs supported on EXTEND were delivered and sacrificed on post-EXTEND days 74, 12, and 4, respectively. Globes were harvested, fixed in 10% formalin, and bisected. Four H&E slides per globe were examined.

Results : Control eyes demonstrated appropriate retinal development and vasculature for gestational age. Experimental eyes revealed the presence of all retinal layers with vasculature extending to the peripheral retina and outer plexiform layer. Retinas were most developed in lambs supported the longest on EXTEND, while others exhibited thinner inner retinal layers.

Conclusions : EXTEND promotes normal development of fetal lambs that correspond to 23-25 weeks gestation in humans. The impact of an artificial womb on retinal development was previously unknown. Microscopic examination revealed normal retinal architecture in lambs supported by EXTEND. Interestingly, the most developed retinas were seen in lambs supported the longest on EXTEND, while the lamb supported the shortest demonstrated a less mature retina for age. This finding suggests that the length of time spent in the artificial womb may promote normal retinal development. Further investigation is warranted to determine the applicability of these findings to the development of the visual system in human infants.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1 A. EXTEND configuration; B-D. Photomicrographs of control retina at 135d after conception (B); retinas supported on EXTEND for 20d, post-EXTEND for 74d (C); and EXTEND for 29d, post-EXTEND 12d (D); brackets highlight inner nuclear layer; all images, H&E 20X.