Normal retinal vascularization in humans commences around weeks 16 to 17 gestational age (GA) and grows centrifugally at 0.1 mm/week to almost reach the margins of the retina at birth.
7 The eye in some nonprimate mammals with holangiotic retinae is less mature at birth and retinal vascularization is often incomplete compared to the precocial state in the human eye. Researchers have exploited this situation by exposing newborn or very young animals, including cats, dogs, rats, and rabbits, to hyperoxic conditions at birth to “mimic” the human premature infant.
2,5,8,9 As the high O
2 exposure occurs at term, the pathology in these models is referred to as oxygen-induced retinopathy (OIR).
10 At birth, mice still have a functioning and prominent hyaloid vasculature and the retina is largely avascular. Superficial vessels growing radially from the optic nerve head to reach the retinal margin by postnatal day 8 (P8) coincide with regression of hyaloid vasculature.
11 Vertical sprouting occurs around P7 to form deep and intermediate plexi of capillaries, a process that continues centrifugally to reach the retinal margins between P12 and P15.
12 This process is roughly analogous to the manner in which retinal vascularization occurs in humans in the third trimester. The timing of hyperoxia exposure between P7 and P12 in the well-described OIR mouse model
13,14 was chosen to mimic the equivalent stage of ocular development in very preterm or moderate-preterm human infants. In this model, mouse pups are exposed to 75% oxygen between P7 and P12 and when examined around P17 to P21, the retina is characterized by a central quantifiable zone of avascularity and patches of neovascular tufts breaching the inner limiting membrane in the midperipheral retina and entering the vitreous, both resembling to some extent features of human ROP.
13,14 Several pathognomonic features of severe (stage 4, 5) ROP such as retinal detachment, vitreous hemorrhages, cicatricial changes (retinal scarring), and avascularity of peripheral retina are not a feature of this model.
11,15,16 Secondly, electroretinographic studies have shown that both photoreceptor (a-wave) and bipolar cell (b-wave) function while significantly reduced at P18
17 have largely recovered by 8 weeks.
18 Lastly, the hyaloid system has regressed as normal by week 5, and the retina and its vasculature, despite the earlier disturbances, are described as normal.
14,17,19