Tenascin-C is a large hexameric extracellular matrix glycoprotein that modulates cellular growth and adhesion. Tenascin-C is associated with angiogenesis (1,2) and has been detected in the epiretinal membranes of patients with proliferative diabetic retinopathy (PDR) (3). There are no reports, however, on the vitreous concentration of tenascin-C. In this study, we investigated the vitreous of patients with PDR for the presence of tenascin-C.

We assayed tenascin-C levels in vitreous samples from 108 consecutive patients with either PDR (58 patients) or macular hole or idiopathic epimacular membrane (nondiabetic control subjects, 50 patients) who underwent pars plana vitrectomy. In all cases, patients who had a recent vitreous hemorrhage were not included. The stage of PDR was classified as active (33 patients) if there were new preretinal capillaries and as quiescent (25 patients) if the vasoproliferation consisted of only large vessels within the membrane (4,5). Informed consent was obtained from each patient. The undiluted vitreous samples were collected during the pars plana vitrectomy before intraocular infusion. Enzyme-linked immunosorbent assay was used to determine vitreous tenascin-C concentrations as previously described (6). The total protein concentration of the vitreous samples was measured using a commercial assay (Pierce Chemical, Rockford, IL). The Mann-Whitney U test was used to compare vitreous concentrations of protein and tenascin-C.

There was no significant difference in intravitreous protein levels (median range) between patients with PDR (3.35 mg/ml, range 0.91–9.12) and control subjects (2.41 mg/ml, 0.92–9.31) (P = 0.1287). Tenascin-C levels in PDR (761.0 ng/ml, 12.0–1330.0) were significantly higher than in the control subjects (18.7 ng/ml, 9.9–713.0) (P < 0.0001). Moreover, the differences remained highly significant (P < 0.0001) when the ratio of tenascin-C to protein was considered (PDR 237.9, 2.1–926.5; control subjects 8.2, 1.6–136.3) (5,7).

Intravitreous tenascin-C concentrations in active PDR patients were significantly higher than those in quiescent PDR patients in absolute terms (777.0 ng/ml, 729.0–1330.0 vs. 761.0 ng/ml, 12.0–1030.0; P = 0.0334). The differences remained significant when the ratio of tenascin-C to protein was considered (308.9, 85.0–926.5 vs. 168.0, 2.1–671.7; P = 0.0074).

Neovascularization is the most important event in PDR. Tenascin-C is involved in the sprouting of endothelial cells, which is a necessary step in angiogenesis (1). Jallo et al. (2) reported that tenascin-C is associated with vessel formation in brain tumors. Tenascin-C mRNA expression significantly increases in diabetic retinopathy retina compared with normal retina (8) and has been detected in the epiretinal membranes of PDR (3). Our results are consistent with these previous reports, implicating tenascin-C in the pathophysiology of PDR.

In conclusion, vitreous levels of tenascin-C increase in PDR patients and tenascin-C levels are elevated in the active PDR stage. These results indicate that tenascin-C might be involved in the pathogenesis of PDR.

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Address correspondence to Yoshinori Mitamura, Department of Ophthalmology, School of Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan. E-mail: ymita@sapmed.ac.jp.