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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Invest+Ophthalmol+Vis+Sci
2014 ; 55
(4
): 2516-25
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Endothelin receptor-A antagonist attenuates retinal vascular and neuroretinal
pathology in diabetic mice
#MMPMID24644048
Chou JC
; Rollins SD
; Ye M
; Batlle D
; Fawzi AA
Invest Ophthalmol Vis Sci
2014[Apr]; 55
(4
): 2516-25
PMID24644048
show ga
PURPOSE: We sought to determine the effects of atrasentan, a selective
endothelin-A receptor antagonist, on the retinal vascular and structural
integrity in a db/db mouse, an animal model of type 2 diabetes and diabetic
retinopathy. METHODS: Diabetic mice, 23 weeks old, were given either atrasentan
or vehicle treatment in drinking water for 8 weeks. At the end of the treatment
period, eyes underwent trypsin digest to assess the retinal vascular pathology
focusing on capillary degeneration, endothelial cell, and pericyte loss.
Paraffin-embedded retinal cross sections were used to evaluate retinal sublayer
thickness both near the optic nerve and in the retinal periphery.
Immunohistochemistry and TUNEL assay were done to evaluate retinal cellular and
vascular apoptosis. RESULTS: Compared with untreated db/db mice, atrasentan
treatment was able to ameliorate the retinal vascular pathology by reducing
pericyte loss (29.2% ± 0.4% vs. 44.4% ± 2.0%, respectively, P < 0.05) and
capillary degeneration as determined by the percentage of acellular capillaries
(8.6% ± 0.3% vs. 3.3% ± 0.41%, respectively, P < 0.05). A reduction in inner
retinal thinning both at the optic nerve and at the periphery in treated diabetic
mice was also observed in db/db mice treated with atrasentan as compared with
untreated db/db mice (P < 0.05). TUNEL assay suggested that atrasentan may
decrease enhanced apoptosis in neuroretinal layers and vascular pericytes in the
db/db mice. CONCLUSIONS: Endothelin-A receptor blockade using atrasentan
significantly reduces the vascular and neuroretinal complications in diabetic
mice. Endothelin-A receptor blockade is a promising therapeutic target in
diabetic retinopathy.