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Abstract Sildenafil citrate is one of the most commonly used drugs worldwide and the drug has proved its great effect in treatment of erectile dysfunction in men of different ages, but it has been found that the drug has multiple adverse effects which appear when the drug used in high doses and for long duration. These adverse effects include headache hypotension, facial flushing, indigestion and nasal congestion. It has been found that one of the most important adverse effects of sildenafil is non artertic anterior ischemic optic neuropathy (NAION) which appears in the form of sudden painless loss of vision which has been spread greatly between users of the drug. WHO reports a large number of NAION cases of different ages every year but most of these cases are old age who suffer from diabetes mellitus, atherosclerosis, hypotension or hypercholestramia which considered to be important risk factors for development of the disease. Multiple studies have discussed the causal relation between usage of sildenafil citrate and development of NAION but all these studies concentrated on the clinical aspects of the disease, so the main aim of this study was focusing on the histological changes induced by application of sildenafil citrate on adult and senile optic nerve of albino rats. Twenty four rats had been used in this study and they were divided into 4 groups:- Group1 (adult control group): this group consisted of 6 adult rats, they received oral DMSO,.2% for 30 days. - Group2 (senile control group): this group consisted of 6 senile rats, they received oral DMSO,.2% For 30 days. - Group3 (adult experimental group): this group consisted of 6 adult rats, they received oral sildenafil citrate 1.43mg/kg dissolved in DMSO,.2% for 30 days. - Group4 (senile experimental group): this group consisted of 6 senile rats, they received oral sildenafil citrate 1.43mg/kg dissolved in DMSO,.2% for 30 days. The rats were sacrificed after 4 weeks and the optic nerve was dissected and fixed in 10% formaldehyde for H&E and luxol fast blue stain and glutraldhyde 2% for semithin sections, Epon blocks and toludine blue stain. When samples are examined it revealed that: By examination of H&E sections, the adult control group revealed that the optic nerve consisted of nerve fibers and each one of them surrounded by oligodendrocytes, nuclei of astrocytes in between, the nerve surrounded by three meningeal layers arranged from outside to inside dura matter, pia matter and arachnoid matter. The pia matter sends pial septa to separate the nerve fibers from each other. In comparison with control group, the adult experimental group revealed marked change in the shape of the nuclei of oligodendrocytes which became flattened and elongated increased spaces between nerve fibers, marked pleomorphism which indicate occurrence of atrophy and degeneration of some nerve fibers and there were some vacuolations started to appear. The control senile group revealed some histological changes such as widened spaces between nerve fibers and some vacuolations which possibly induced by aging. In comparison with the senile control group The experimental group revealed marked decrease in number of oligodendrocytes, change in the shape of their nuclei which became flattened, in addition to marked swelling of nerve fibers and marked pleomorphism Luxol fast blue stain for senile control group gave the same results which were shown with H&E stain in the adult control group, but it revealed drastic changes in the senile experimental group as extensive large sized vacuoles, marked patches of degeneration and deeply stained nuclei of oligodendrocytes. Examination of semithin sections of the control adult and senile groups revealed tightly packed axon bundles surrounded by individual thin septa. The myelinated nerve fibers each one surrounded by its own myelin sheath and nuclei of oligodendrocytes. After treatment, and in comparison with the control group the experimental adult group showed extensive areas of degeneration, the nerve fibers lose their myelin sheaths in some areas, while the healthy nerve bundles appear irregular with their myelin sheaths also there is a marked pleomorphism.The semithin sections of the senile experimental group revealed extensive areas of degeneration; loss of myelinated axons, large sized vacuoles and marked pleomorphism in comparison with the senile control group. Significant numbers of inflammatory cells accumulate within the ischemic area, primary infarct area. Extrinsic macrophages (blood-borne macrophages which invade the damaged tissue) are identifiable early in their generation by the presence of ED1 (CD68) protein. The present study showed an increased number and size of astrocytes as detected by GFAP stained sections and presence of activated microglia which in the treated groups more than the control groups and showed marked increase in size and number and thickness of their cytoplasmic processes Finally, this study revealed that the usage of sildenafil citrate drug in high doses or for prolonged duration has a great effect on the histology of optic nerve through decrease of blood flow in the short posterior ciliary arteries causing atrophy and degeneration of optic nerve fibers and affecting the visual acuity of the patients. |