TY - JOUR
T1 - Connective tissue growth factor is involved in structural retinal vascular changes in long-term experimental diabetes
AU - van Geest, Rob J.
AU - Leeuwis, Jan Willem
AU - Dendooven, Amélie
AU - Pfister, Frederick
AU - Bosch, Klazien
AU - Hoeben, Kees A.
AU - Vogels, Ilse M. C.
AU - van der Giezen, Dionne M.
AU - Dietrich, Nadine
AU - Hammes, Hans-Peter
AU - Goldschmeding, Roel
AU - Klaassen, Ingeborg
AU - van Noorden, Cornelis J. F.
AU - Schlingemann, Reinier O.
PY - 2014
Y1 - 2014
N2 - 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
AB - 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
U2 - https://doi.org/10.1369/0022155413512656
DO - https://doi.org/10.1369/0022155413512656
M3 - Article
C2 - 24217924
SN - 0022-1554
VL - 62
SP - 109
EP - 118
JO - Journal of Histochemistry and Cytochemistry
JF - Journal of Histochemistry and Cytochemistry
IS - 2
ER -