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 The retina of the Control group showed the different layers from the scleral to vitreal side; the
retinal pigmented epithelium, the photoreceptor cell layer that was formed of lightly stained
outer segments and deeply stained inner segments, the outer limiting membrane. The outer
nuclear layer that was contained packed densely stained rods and cones nuclei. The outer
plexiform appeared much thinner than the inner plexiform layer and both had a reticular
appearance. The inner nuclear layer was thinner than the outer nuclear one and its cells were
fewer and vary in shape, size and density. The ganglion cell layer contained the cell bodies of
ganglion cells that were arranged in a non-continuous row and had large oval vesicular nuclei.
The nerve fiber layer was thin and formed of ganglion cell axons. The innermost layer was the
inner limiting membrane (Fig. 1A).
Tadalafil group displayed detachment of the retinal pigmented epithelium. The mean total
retinal thickness and the mean thickness of outer and inner nuclear layers were significantly
reduced (P<0.05) compared to Control group. The photoreceptors outer segment showed vacuolations and the outer limiting membrane was interrupted. Moreover, there were disorganization of outer plexiform layer and diminished cell population of outer and inner nuclear layers with empty spaces between their cells. Many congested dilated blood capillaries were observed in the inner nuclear and ganglion cell layers. The ganglion cell layer appeared with few ganglion cells (Figs. 1B, 2 A-C). The mean number of ganglion cells /100 µm of ganglion cell layer length showed a significant decline (P<0.05) compared to the Control group (Fig.3). Withdrawal group revealed better histological structure of the retina. The mean total retinal thickness and the mean thickness of outer and inner nuclear layers were significantly greater (P<0.05) compared to Tadalafil group but still smaller than control group. Intact retinal pigment epithelium was noted. Increased cell population in outer and inner nuclear and ganglion cell layer was noticed (Figs.1C, 2 A-C). The mean number of ganglion cells /100 µm of ganglion cell layer length was significantly higher (P< 0.05) than Tadalafil group but still lower than Control group (Fig. 3). Immunohistochemical stains PDE5 Examination of PDE5 immunohistochemically stained sections in the Control group exhibited strong positive immune reaction in the pigmented epithelium, inner segment of photoreceptors, outer and inner plexiform layers, cells of inner nuclear and ganglion cell layers and the lining endothelial cells of capillaries in ganglion cell layer (Fig.4A). On the other hand, Tadalafil group showed a weak positive reaction in the pigmented epithelium, inner segment of photoreceptors, outer and inner plexiform layers. A weak to moderate reaction in inner nuclear and ganglion cell layers and capillary endothelium in ganglion cell layer were also noticed (Fig. 4B). In Withdrawal group, there was an upregulation of PDE5 immunoreactivity at the same previously mentioned retinal layers and the capillary endothelium (Fig. 4C).The mean percent area of PDE5 immunoexpression was significantly reduced (P<0.05) in Tadalafil group compared to Control group. While it was significantly higher (P< 0.05) in Withdrawal group compared to Tadalafil group but still lower than Control group (Fig.5). Bcl-2 The Control group showed moderate to strong Bcl-2 immuoexpression in the retinal pigmented epithelium, photoreceptors, outer and inner plexiform layers, some cells and capillary endothelium of inner nuclear and Ganglion cell Layers (Fig. 6A). Tadalafil group revealed a negative Bcl-2 immuoexpression in all retinal layers. However, strong reaction was observed only in the capillary endothelium of inner nuclear and ganglion cell layers (Fig. 6B). On the other hand, in Withdrawal group, restoration of Bcl-2 immunoexpression was observed in the photoreceptors, outer and inner plexiform layers. The capillary endothelium of inner nuclear layer also showed strong Bcl-2 expression (Fig. 6C). The mean percent area of Bcl-2 immunoexpression showed a significant reduction (P<0.05) in Tadalafil group compared to control group and was significantly higher (P<0.05) in Withdrawal group compared to 

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