FT011M reduced acellular capillaries and extracellular matrix proteins in retina from Ren-2 rats diabetic for 32 weeks.

<p>Non-diab, non-diabetic. Diab, diabetic. V, vehicle. Stain, Periodic acid-Schiff’s reagent. Bar, 40 μm. (A to C) In diab + V, acellular capillaries (asterisk) were increased in all regions of retina compared to non-diabetic + V. In diabetic rats, FT011M reduced acellular capillaries in all regions of the retina. Arrow, pericyte ghost. (D to G) *P < 0.05 to non-diab + V. #P < 0.05 to diab + V. N = 8 to 11 rats per group. (H) Collagen IV mRNA levels in retina. (I) Fibronectin mRNA levels in retina. *P < 0.05, **P < 0.01 to non-diab + V. ###P < 0.001 to diab + V. N = 5 to 9 rats per group. Values are Mean±SEM.</p

FT011M reduced Iba1-immunolabeled microglia in the retina of Ren-2 rats diabetic for 8 weeks.

<p>Non-diab, non-diabetic. Diab, diabetic. V, vehicle. Three-μm paraffin sections. ILM, inner limiting membrane. GCL, ganglion cell layer. IPL, inner plexiform layer. INL, inner nuclear layer. Counterstain, haematoxylin. Original magnification, 400X. Bar, 40 μm. (A to C) In diab + V, Iba1 immunolabeling (arrowheads) was increased compared to non-diab + V. In diabetic rats, FT011M reduced Iba1 immunolabeling to the level of non-diab + V. (D) **P < 0.01 to non-diab + V. ##P < 0.01 to diab + V. N = 4 to 6 rats per group. Values are Mean ± SEM.</p

Animal characteristics.

<p>*P < 0.05 versus control. N = 8 rats per group. Values are mean ± SEM.</p><p>Animal characteristics.</p

Representative images for myocyte hypertrophy.

<p>(A) Diabetic rats demonstrated myocyte hypertrophy as evidenced by increased cross sectional area when compared with control rats. Treatment with DiOHF reduced cross sectional area in diabetic rats but had no effect on control rats. (B) Quantitative data for myocyte cross sectional area. *<i>P</i>&lt;0.05 vs control (non-diabetic) rats; †<i>P</i>&lt;0.05 vs diabetic rats. Original magnification ×200.</p

Representative pressure volume (PV) loops during preload reduction.

<p>Note the steeper slope of EDPVR (green line) and rightward shift in the diabetic group (C) compared to control (A). An increase in the slope of EDPVR indicated decreased chamber compliance as seen in the diabetic animals which was reduced with DiOHF treatment (D). *<i>P</i>&lt;0.05 vs control (non-diabetic) rats; †<i>P</i>&lt;0.05 vs diabetic rats.</p

Immumohistochemistry staining for collagen type I.

<p>(A) Representative images. Brown region represents positive immunostaining for collagen type I which was substantially increased in diabetic rats and reduced by DiOHF treatment. The amount of collagen type I was found to be similar in control and control-treated rats. Collagen type I interstitial accumulation as assessed by percentage proportional area showing positive immunostaining in control and diabetic rats treated with or without DiOHF (B). Data expressed as mean ± SE. *<i>P</i>&lt;0.05 vs control (non-diabetic) rats; †<i>P</i>&lt;0.05 vs diabetic rats. Original magnification ×200.</p

Txnip protein expression.

<p>(A) Representative western blot and (B) quantitation of Txnip normalized to loading control pan-actin. The significant increase in Txnip protein in diabetic rats was moderately reduced by DiOHF treatment. Data expressed as mean ± SE. *<i>P</i>&lt;0.05 vs control (non-diabetic) rats.</p

FT011M reduced Müller cell gliosis in the retina of Ren-2 rats diabetic for 8 weeks.

<p>Non-diab, non-diabetic. Diab, diabetic. V, vehicle. Three-μm paraffin sections. IPL, inner plexiform layer. INL, inner nuclear layer. OPL, outer plexiform layer. ONL, outer nuclear layer. Original magnification, 400X. Bar, 40 μm. (A to C) Central retina. (D to F) Mid retina. (G to I) Peripheral retina. In non-diab + V, GFAP immunolabeling is present on the retinal surface (asterisk) and in Müller cell processes (arrows) extending throughout the retinal layers and in the central, mid and peripheral retina (A, D, G). GFAP immunolabeling is increased in diab + V (B, E, H). In diabetic rats, FT011M reduced GFAP immunolabeling in the central (G), mid (F) and peripheral (I) retina to the level of non-diab + V. (J to M) *P < 0.01 and ***P < 0.001 to non-diab + V. ##P < 0.01 and ###P < 0.001 to diab + V. N = 4 to 6 rats per group. Values are Mean ± SEM.</p

FT011M reduced VEGF immunolabeling in retina of Ren-2 rats diabetic for 8 weeks.

<p>Non-diab, non-diabetic. Diab, diabetic. V, vehicle. Three-μm paraffin sections. GCL, ganglion cell layer. IPL, inner plexiform layer. INL, inner nuclear layer. ONL, outer nuclear layer. Counterstain, haematoxylin. (A). In non-diab + V, VEGF immunolabeling is occasionally detected in ganglion cells (arrowheads) in the GCL. (B) In diab + V, VEGF immunolabeling is increased compared to non-diab + V and detected in ganglion cells and Müller cell processes (arrows) extending throughout the retina. Inset showing higher powered image of Müller cell processes. (C) In diabetic rats treated with FT011M, VEGF immunolabeling was reduced to the level of non-diab + V. (A to C) Original magnification, 400X. Bar, 40 μm. Inset: Bar, 75 μm. (D) **P < 0.01 to non-diab + V. ##P < 0.01 to diab + V. N = 4 to 6 rats per group. Values are Mean ± SEM.</p

Renal tubular expression of kidney injury molecule-1 (KIM-1) and correlation with serum IS levels.

<p>Increased tubular expression of KIM-1 was observed in MI+Vehicle animals, AST-120 treatment significantly reduced KIM-1 expression to sham levels (A). Serum IS was significantly and positively correlated with KIM-1 expression (B, p&lt;0.01), *p&lt;0.05 vs Sham. ^##p&lt;0.01 vs MI+Vehicle.</p