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IGF-I Is Critical for Normal Vascularization of the Human Retina

Department of Clinical Neurosciences (A.H.), Section of Ophthalmology, Department of Pediatrics (A.H., A.K., K.A.W.), International Pediatric Growth Research Centre, Department of Internal Medicine (B.C.), Research Center for Endocrinology and Metabolism, Sahlgrenska Academy of Göteborg University, S-416 85 Göteborg, Sweden; Mälarsjukhuset (K.S.), S-631 88 Eskilstuna, Sweden; Pediatric Endocrinology Unit (M.B., L.D.), Federal University of Parana, Curitiba 80430-040, Brazil; Department of Endocrinology (M.S.), Sankt Bartholomews, EC1A 7BE London, United Kingdom; Department of Biostatistics (E.S.), Örebro University, S-701 82 Örebro, Sweden; Harvard Medical School (L.S.), Boston, Massachusetts 02115; and Department of Ophthalmology (D.W.), Rabin Medical Center, Beilinson Campus, Unit of Endocrinology and Diabetes Research (Z.L.), Schneider Children’s Medical Center, Tel Aviv University, 49202 Tel Aviv, Israel

Address all correspondence and requests for reprints to: Ann Hellström, Section of Pediatric Ophthalmology, The Queen Silvia Children’s Hospital, Sahlgrenska Academy of Göteborg University, S-416 85 Göteborg, Sweden. E-mail: . ann.hellstrom{at}medfak.gu.se

Abstract

Experimental and clinical studies suggest that GH and IGF-I may be involved in neovascularization of the retina in diabetes and retinopathy of prematurity. However, the role of GH and IGF-I has not been well established in normal retinal vessel development in humans. Therefore, we examined retinal vessel morphology by digital image analysis of ocular fundus photographs in 13 patients with genetic defects of the GH/IGF-I axis and low levels of IGF-I during and after normal retinal vessel growth. Eleven patients (four females and seven males aged 10–49 yr) had defects of the GH receptor (Laron syndrome). One male (20 yr) had a partial deletion of the IGF-I gene, and one female (14 yr) had a single allele deletion of the IGF-I receptor gene. Patients with defects in the GH/IGF-I axis had significantly less retinal vascularization as evidenced by lower number of vascular branching points (median 23, range 16–25), compared with the reference group of 100 normal controls (median 28, range 19–40, P < 0.001). All 13 individuals had vascular branching points below the median of the reference group. This is the first study to provide genetic evidence for a role of the GH and IGF-I system in retinal vascularization in humans.

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