Retinal neovascular markers in retinopathy of prematurity: aetiological implications

Abstract

Aim: (1) To determine if expression of the blood-tissue barrier associated glucose transporter GLUT1 is preserved by the neovasculature of retinopathy of prematurity (ROP), in contrast with the reported loss of GLUT1 expression in preretinal vessels of proliferative diabetic retinopathy. (2) To compare the vascular immunophenotype of ROP to juvenile haemangioma, another perinatal neovascular disorder that has recently been shown to express placental type vascular antigens, including GLUT1 and Lewis Y antigen.

Methods: A retrospective case report was carried out. Immunoreactivities for GLUT1 and Lewis Y antigen were assessed in a human eye with stage 3 ROP and compared with those in a control (paediatric) eye. The presence or absence of endothelial GLUT1 and Lewis Y immunoreactivity was determined in preretinal and intraretinal vessels.

Results: Immunoreactivity was positive for GLUT1 and negative for Lewis Y in the intraretinal and preretinal neovasculature of the ROP affected eye and in the normal retinal vessels of the control eye.

Conclusions: Retention of immunoreactivity for GLUT1 distinguishes ROP from proliferative diabetic retinopathy. Furthermore, absence of Lewis Y antigen co-expression distinguishes ROP from juvenile haemangioma, a perinatal form of GLUT1 positive neovascularisation that has recently been linked to placental vasculature.

Figure 1

Haematoxylin and eosin stained section of the temporal retina in the left eye showing marked intraretinal neovascularisation, extending into the vitreous within a thin preretinal membrane (open arrow). Note the focal haemorrhage (black arrow). (Original magnification ×200.)

Figure 2

GLUT1 immunoreaction of the ROP affected temporal retina in the left eye. Strong endothelial GLUT1 immunopositivity was present in both the preretinal (arrows) and intraretinal (arrowheads) neovasculature. GLUT1 immunopositivity was also seen in the nerve fibre and cell body layers. (DAB+ chromagen; original magnification ×400.)

Figure 3

GLUT1 immunoreaction in uninvolved retina, optic nerve, ciliary muscle, and iris of control (A–D) and ROP affected (E–H) eye. Strong capillary endothelial GLUT1 immunoreactivity (black arrows) was present within the uninvolved retina (A, E), optic nerve (B, F), ciliary muscle (C, G), and iris (D, H) of both the control and ROP affected eye. Use of red VIP chromagen in B–D, as opposed to brown DAB+ chromagen (A, E–H), allowed clear distinction of specific GLUT1 immunoreaction (red colour) from the brown pigment normally abundant in the iris and retinal/ciliary epithelium. Note the red GLUT1 immunoreaction of the non-pigmented epithelial layer of the ciliary muscle (C, open arrow), overlying the pigmented layer. Intraluminal erythrocytes (E, asterisk) served as internal positive controls for GLUT1. Original magnifications ×200 (A–C, F, H) and ×400 (D, E, G.)

Figure 4

Lewis Y antigen (LeY) immunoreaction of control eye (A), ROP affected eye (B), and juvenile haemangioma (C). Microvessels of both the normal (A, black arrows) and ROP affected eye (B, intraretinal neovascularisation—open arrow; intravitreous neovascularisation—black arrows) lacked LeY immunoreactivity, as did choroidal vessels, shown for the normal eye (A, open arrows). In contrast, strong endothelial LeY immunopositivity was present in this early involutional juvenile haemangioma (C). Original magnifications ×200 (A) and ×400 (B, C).