Connective tissue growth factor is involved in structural retinal vascular changes in long-term experimental diabetes

Rob J Van Geest, Jan Willem Leeuwis, Amélie Dendooven, Frederick Pfister, Klazien Bosch, Kees A Hoeben, Ilse M C Vogels, Dionne M Van der Giezen, Nadine Dietrich, Hans-Peter Hammes, Roel Goldschmeding, Ingeborg Klaassen, Cornelis J F Van Noorden, Reinier O Schlingemann

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

Early retinal vascular changes in the development of diabetic retinopathy (DR) include capillary basal lamina (BL) thickening, pericyte loss and the development of acellular capillaries. Expression of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family member CCN2 or connective tissue growth factor (CTGF), a potent inducer of the expression of BL components, is upregulated early in diabetes. Diabetic mice lacking one functional CTGF allele (CTGF⁺/⁻) do not show this BL thickening. As early events in DR may be interrelated, we hypothesized that CTGF plays a role in the pathological changes of retinal capillaries other than BL thickening. We studied the effects of long-term (6-8 months) streptozotocin-induced diabetes on retinal capillary BL thickness, numbers of pericytes and the development of acellular capillaries in wild type and CTGF⁺/⁻ mice. Our results show that an absence of BL thickening of retinal capillaries in long-term diabetic CTGF⁺/⁻ mice is associated with reduced pericyte dropout and reduced formation of acellular capillaries. We conclude that CTGF is involved in structural retinal vascular changes in diabetic rodents. Inhibition of CTGF in the eye may therefore be protective against the development of DR.

Originele taal-2Engels
Pagina's (van-tot)109-18
Aantal pagina's10
TijdschriftJournal of Histochemistry & Cytochemistry
Volume62
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - feb. 2014

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