Age-dependent alteration of intraocular soluble heparan sulfate levels and its implications for proliferative diabetic retinopathy

Koji M. Nishiguchi, Hiroaki Ushida, Daisuke Tomida, Shu Kachi, Mineo Kondo, Hiroko Terasaki

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9 Citations (Scopus)


Purpose: To assess the relationship between intraocular soluble heparan sulfate (HS) concentration and age in subjects with and without diabetic retinopathy. Methods: Vitreous from subjects with idiopathic maculopathies (n=17), i.e., macula hole or epiretinal membrane, or nonproliferative diabetic retinopathy (non-PDR; n=5) and aqueous humor from subjects with PDR (n=16), non-PDR (n=7), or cataracts (n=15) was collected. The levels of HS and vascular endothelial growth factor (VEGF) were measured using enzyme-linked immunosorbent assay. Concentrations of sulfated glycosaminoglycan were determined through dimethylmethylene blue-based assay. The effect of the vitreal HS level on the binding of exogenous VEGF to surface-bound heparin was determined in vitro. Results: The level of HS in vitreous samples from subjects with idiopathic maculopathies increased concomitantly with age (p=0.020, R2=0.327). Meanwhile, HS levels in aqueous humor were lower in PDR subjects than in non-PDR (p=0.003) and cataract subjects (p=0.007). However, the PDR subjects were signifcantly younger than the non-PDR subjects (p<0.001) or cataract subjects (p<0.001). When the three groups were controlled for age, the levels of HS glycosaminoglycans were no longer different between the three (p=0.247). The increasing level of HS or sulfated gly-cosaminoglycan in the vitreous was associated with its increased inhibitory effect on interaction between VEGF and surface heparin in vitro (p=0.014, R2=0.377). Conclusions: The HS level of the intraocular fuid increased with age. The possible link between low HS in intraocular fuid and increased localization of VEGF at the retinal surface may provide one explanation for the higher susceptibility of younger subjects with diabetes mellitus to developing PDR.

Original languageEnglish
Pages (from-to)1125-1131
Number of pages7
JournalMolecular vision
Publication statusPublished - 2013 Jun 6
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology


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