Andréia Vitor Couto do Amaral

Functional and Structural Evaluation of Sildenafil in a Rat Model of Acute Retinal Ischemia/Reperfusion Injury.

ABSTRACT Purpose: Retinal ischemia is a common cause of visual impairment and blindness. Sildenafil, a PDE5 inhibitor which inhibits cGMP degradation and in turn prolongs the effect of nitric oxide, has been shown to be protective in a number of ischemia/reperfusion (I/R) injuries, as well as in neuronal damage. We hypothesized that treatment with sildenafil might be neuroprotective in a model of acute retinal I/R injury. Methods: Anterior chamber cannulation was performed to induce unilateral I/R injury in 38 Lewis rats. Animals received intraperitoneal injections of sildenafil (0.5 and 1 mg/kg once a day, for a period of 7 and 18 days, respectively), or saline. Electroretinography recordings, retinal ganglion cell (RGC) counts following retrograde labeling with fluorogold, histopathology, and immunohistochemistry (IHC) using antibodies against PDE5, NOS2, caspase-3, caspase-9, and Bcl-2 were conducted. Results: No significant differences in electroretinography, RGC counts, or retinal morphometry were observed between experimental eyes of sildenafil- and saline-treated animals. A tendency toward less necrosis in histopathology, and a slight trend toward lower PDE5, NOS2, and caspase-9 and higher Bcl-2 IHC scores were evident in experimental retinas of sildenafil-treated animals. Conclusions: Electroretinography, RGC counts, and retinal morphometry failed to show any neuroprotective effect of sildenafil in acute retinal I/R injury in rats. A slight positive effect of sildenafil was qualitatively indicated by histopathology and IHC.

Electroretinography and immunohistochemistry of retina in rabbits treated with sildenafil citrate

Sildenafil citrate is a type-5 phosphodiesterase inhibitor (PDE-5), able to inhibit type-6 phosphodiesterase (PDE-6) as well, providing clinical benefits and paraeffects, some of them potentially related to the retina. The effects of the sildenafil on the retrobulbar and retinal circulation were studied in 27 adult male rabbits of the White New Zealand breed. The electric activity of the retina was evaluated before and at the end of the treatments, and immunohistochemistry studies were conducted. An amplitude increase of the b wave was found in the mixed response of cones and rods after 7 days of treatment with sildenafil citrate. However, in the other evaluations and periods, the values did not differ from the basal ones. Through immunohistochemistry, no significant decrease of the expression of PDE-5 and PDE-6 proteins was observed. Based on the results obtained, it is possible to admit that the sildenafil citrate did not change the expression of PDE-5 and PDE-6, neither the electroretinographic activity of the retina of male rabbits of the White New Zealand breed.

Estudo clínico e histológico das pálpebras e conjuntiva hígidas submetidas ao tratamento tópico com soluções anestésicas em coelhos

This work aimed to evaluate commercial presentations of anesthetic eye drops in sixty three New Zealand rabbits which were separated equally in three groups (G1, G2 and G3). The G1 group was treated with 0.5% proparacaine chloridrate eye drop, G2 group with 1% tetracaine chloridrate associated with 0.1% phenylephrine eye drop and G3 group with 0.9% physiologic solution eye drop. All of them received one drop in each eye six times a day. Each group was subdivided into three subgroups (seven rabbits), which are treated for 3, 7 and 15 days. At the end of each treatment, two animals in each subgroup were subject to euthanasia, for the purpose of conjunctiva, eyelids and third eyelids histological evaluation. At the clinical exam, different grades of episcleritis were found in all rabbits in G2 group and only in 17.8% of the rabbits in G1 group. Eye and eyelid histologic evaluation of G2 group revealed an upgrade of goblet cells and eosinophil number, lymphoid follicle proliferation and increase of interstitial space in the eyelids. We could conclude that 1% tetracaine associated with 0.1% phenylephrine eye drop caused more eyelid and ocular conjunctiva toxicity than 0.5% proparacaine eye drop.