Elsevier

Ophthalmology

Volume 105, Issue 3, 1 March 1998, Pages 412-416
Ophthalmology

Vascular endothelial growth factor upregulation in human central retinal vein occlusion1

https://doi.org/10.1016/S0161-6420(98)93020-2Get rights and content

Abstract

Background and objective

Vascular endothelial growth factor (VEGF), a key mediator of intraocular neovascularization, is triggered by hypoxia and has been shown in the eyes of animal models of central retinal vein occlusion (CRVO). However, there is little information on CRVO in humans, in particular, the identity of VEGF-producing cells.

Study design

The study design was molecular localization of the site of VEGF production in the eyes of patients with CRVO.

Participants

Ten formaldehyde solution-fixed and paraffin-embedded eyes removed surgically from patients with CRVO and neovascular glaucoma were studied. Five eyes with uveal melanoma and no neovascularization served as control specimens.

Methods

Thin whole-eye sections were hybridized in situ with a VEGF-specific probe to identify cells producing VEGF messenger RNA (mRNA).

Results

All ten eyes with CRVO showed evidence of intraretinal expression of VEGF mRNA. In all eyes, the inner nuclear layer showed VEGF-upregulated expression. Upregulation of VEGF mRNA was identified in four eyes in the ganglion cell layer and in two eyes with retinal detachment in the outer nuclear layer as well.

Conclusions

The population of VEGF-producing retinal cells in each eye is likely to represent cells residing in ischemic regions of the retina. Hypoxia-induced VEGF is, most likely, the linking factor between retinal ischemia and iris and retinal neovascularization in CRVO.

Section snippets

Materials and methods

The files of the F.C. Blodi Eye Pathology Laboratory at the University of Iowa were searched for paraffin blocks of surgically enucleated eyes with the clinical and histopathologic diagnoses of CRVO and NVG. Cases were excluded if the eyes were phthisical or were complicated by endophthalmitis. Most important, no postmortem specimens were included in this study. Ten eyes were available for study. Five eyes with choroidal or ciliary body melanoma, but with no detectable NV, were analyzed in

Results

The clinical and histologic details of the ten patients included in the study are summarized in Table 1. There were nine women and one man, 70 to 92 years of age (average, 83 years), all with CRVO. There were five right eyes and five left eyes. All were enucleated because of blindness and painful because of NVG. In six of the eyes, vision of “no light perception” was documented. Histologically, all eyes had CRVO and NVG. In these eyes, intraocular hemorrhages were found: in five, anterior

Discussion

The VEGF mRNA expression was upregulated in experimental retinal vein occlusion in rabbits,9 monkeys,14, 16 and murine model.17 We present here, to our knowledge for the first time upregulated expression of VEGF mRNA in a series of human retina with CRVO. Our results, showing that VEGF is upregulated in different layers of the retina in different patients, can be explained by the assumption that VEGF in CRVO is upregulated in response to retinal hypoxia, and in different eyes, different

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    1

    The authors have no proprietary interest in any of the materials used in this study.

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