Connective tissue growth factor is involved in structural retinal vascular changes in long-term experimental diabetes.
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.
Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (RJVG, IMCV, IK, CJFVN, ROS).
Rob J
RJ
Van Geest
Jan Willem
JW
Leeuwis
Amélie
A
Dendooven
Frederick
F
Pfister
Klazien
K
Bosch
Kees A
KA
Hoeben
Ilse M C
IM
Vogels
Dionne M
DM
Van der Giezen
Nadine
N
Dietrich
Hans-Peter
HP
Hammes
Roel
R
Goldschmeding
Ingeborg
I
Klaassen
Cornelis J F
CJ
Van Noorden
Reinier O
RO
Schlingemann
D000818:Animals; D002196:Capillaries / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D057895:Haploinsufficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020286:Pericytes / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
C526318:CCN2 protein, mouse; D055513:Connective Tissue Growth Factor
CCN2; CTGF; acellular capillary; animal model; basal lamina; basement membrane; diabetic retinopathy; pericyte