Tadalafil (Cialis) is one of the most commonly used phosphodiesterase type5 (PDE5) inhibitors. This work aimed to analyze the histological and ultrastructural changes provoked by chronic tadalafil administration in the rat retina, correlate between such changes and PDE5 immunoexpression and to evaluate the possible reversibility of these changes. Thirty Sprague Dawley male rats were randomly distributed into 3 groups. Control group; given 1 ml distilled water daily for 6 weeks. Tadalafil group; given tadalafil in a daily dose of 2.6 mg/kg for 6 weeks. Withdrawal group; given tadalafil 2.6 mg/kg daily for 6 week followed by a withdrawal period of 4 weeks. Retinal specimens were prepared for histological, ultrastructural and immunohistochemical study using anti-PDE5 and anti-Bcl-2 antibodies. Morphometric and statistical studies were performed. Tadalafil group displayed a significant reduction in retinal thickness, diminished cell population of outer and inner nuclear layers, dilated blood capillaries and a significant decline in the number of ganglion cells. Significant reductions of both PDE5 and Bcl-2 immunoexpression were observed. At the ultrastructural level, the photoreceptors showed spacing of outer segments and disorganized membranous discs. Retinal neurons showed ultrastructural degenerative changes in the form of shrunken irregular nuclei, dilated rER, and disrupted mitochondria. Withdrawal group revealed preservation of histological structure and partial restoration of retinal thickness, retinal cells ultrastructure, and PDE5 and Bcl-2 immunoexpressions. In conclusion, chronic use of tadalafil could induce reversible apoptotic and degenerative changes in retinal neurons due to its inhibitory effect on PDE5 expression which affects the metabolism and viability of retinal cells.
Keywords: Bcl-2; Cialis; Immunohistochemistry; PDE5; Retina; Tadalafil; Ultrastructure.
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