A Promising Combination: PACAP and PARP Inhibitor Have Therapeutic Potential in Models of Diabetic and Hypertensive Retinopathies

Figures

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  Figure 1. Representative sections of rat retinas in different conditions: (a) untreated control retina; (b) PACAP-treated control retina; (c) untreated hypertensive retina; (d) PACAP-treated hypertensive retina; (e) untreated diabetic retina; (f) PACAP-treated diabetic retina; (g) PARP inhibitor (Olap)–treated diabetic retina; (h) PACAP- and PARP inhibitor (Olap)–treated diabetic retina; (i) untreated hypertensive diabetic retina (j) PACAP-treated hypertensive diabetic retina; (k) PARP-inhibitor-treated hypertensive diabetic retina; (l) PACAP- and PARP inhibitor (Olap)–treated hypertensive diabetic retina. OLM—outer limiting membrane; ONL—outer nuclear layer; OPL—outer plexiform layer; INL—inner nuclear layer; IPL—inner plexiform layer; GCL—ganglion cell layer; ILM—inner limiting membrane. Arrows indicate capillaries, stars indicate signs of cellular damage.

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  Figure 2. Thickness of OLM–ILM in the PACAP- or/and PARP inhibitor (Olap)–treated and untreated groups of hypertensive and diabetic rat retinas (a,b). Data are presented as mean ± SEM, where *** p < 0.001 and ** p < 0.01, * p < 0.05.

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  Figure 3. Thickness of ONL in the PACAP- or/and PARP inhibitor (Olap)–treated and untreated groups of hypertensive and diabetic rat retinas (a,b). Data are presented as mean ± SEM, where *** p < 0.001 and ** p < 0.01.

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  Figure 4. Thickness of OPL in the PACAP- or/and PARP inhibitor (Olap)–treated and untreated groups of hypertensive and diabetic rat retinas (a,b). Data are presented as mean ± SEM, where * p < 0.05. Representative images of OPL thickness, stained for vGlut1 (c). Scale bar: 50 µm.

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  Figure 5. Thickness of INL in the PACAP- or/and PARP inhibitor (Olap)–treated and untreated groups of hypertensive and diabetic rat retinas (a,b). Data are presented as mean ± SEM, where *** p < 0.001, ** p < 0.01, * p < 0.05.

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  Figure 6. Thickness of IPL in the PACAP- or/and PARP inhibitor (Olap)–treated and untreated groups of hypertensive and diabetic rat retinas (a,b). Data are presented as mean ± SEM, where ** p < 0.01, * p < 0.05. Representative images of the IPL thickness, stained for vGlut1 (c). Scale bar: 50 µm.

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  Figure 7. Number of cells in the ganglion cell layer in the PACAP- or/and PARP inhibitor (Olap)–treated and untreated groups of hypertensive (SHR) and diabetic (STZ) rat retinas (a,b). Cell numbers in ganglion cell layer were measured in retinal sections for lengths of 100 μm. Data are presented as mean ± SEM, where *** p < 0.001, ** p < 0.01, * p < 0.05.

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  Figure 8. Representative retina sections stained with rod bipolar cell marker (PKCα) in different conditions. Inserted images include DAPI staining. (a) Untreated control retina; (b) untreated diabetic retina; (c) PARP inhibitor (Olap)– and PACAP-treated diabetic retina; (d) PARP inhibitor (Olap)– and PACAP-treated hypertensive diabetic retina. INL—inner nuclear layer, IPL—inner plexiform layer. Scale bar: 50 µm.

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  Figure 9. Representative retina sections stained with dopaminergic amacrine cell marker (TH) in different conditions. Inserted images include DAPI staining. (a) Untreated control retina; (b) untreated diabetic retina; (c) PARP inhibitor (Olap)– and PACAP-treated diabetic retina; (d) PARP inhibitor (Olap)– and PACAP-treated hypertensive diabetic retina. INL—inner nuclear layer, IPL—inner plexiform layer. Scale bar: 50 µm.

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  Figure 10. Calbindin immunoreactivity in retina sections under different conditions: (a) untreated control. Inserted images include DAPI staining. (b) Untreated diabetic retina; (c) PACAP- and PARP inhibitor (Olap)–treated diabetic retina; (d) PACAP- and PARP inhibitor (Olap)–treated hypertensive diabetic retina. OPL—outer plexiform layer, INL—inner nuclear layer, IPL—inner plexiform layer, GCL—ganglion cell layer. Scale bar: 50 µm.

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  Figure 11. Calretinin immunoreactivity in retinal sections under different conditions: (a) PACAP-treated control retina. Inserted images include DAPI staining. (b) PACAP-treated hypertensive retina; (c) PACAP-treated diabetic retina; (d) PACAP- and PARP inhibitor (Olap)–treated hypertensive diabetic retina. OPL—outer plexiform layer, INL—inner nuclear layer, IPL—inner plexiform layer, GCL—ganglion cell layer. Scale bar: 50 µm.

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  Figure 12. Parvalbumin immunoreactivity in retinal section with different conditions. Inserted images include DAPI staining. (a) Untreated control; (b) untreated hypertensive retina; (c) PARP inhibitor (Olap)–treated hypertensive diabetic retina; (d) PARP- and PACAP inhibitor (Olap)–treated hypertensive diabetic retina. OPL—outer plexiform layer, INL—inner nuclear layer, IPL—inner plexiform layer, GCL—ganglion cell layer. Scale bar: 50 µm.