Comparison of the Protective Effects of Prostaglandin Analogues in the Ischemia and Reperfusion Model of Rabbit Eyes

Abstract

This study was planned to investigate the neuroprotective potentials of three commercially available prostaglandin analogues (PGA), in the ischemia and reperfusion model (I/R). Thirty New Zealand rabbits were divided into 5 groups and except for the control group (non-ischemic, non-treated), 0.9% NaCl, bimatoprost, latanoprost, or travoprost were applied to both eyes of animals of the respective groups for 1 week. At the end of treatment, ischemia was induced in both eyes of the 4 treatment groups by anterior chamber irrigation of the animals for 60 min. Following 24 h reperfusion, the animals were sacrified. Enucleated eyes and retinal tissues were investigated by light microscopy, electron microscopy, immunohistochemicstry for retinal histopathology, intracellular and apoptotic cells and by retinal morphometry. Vitreous samples were biochemically investigated for probable role of reactive oxygen species, by measuring xanthine oxidase (XO) activity. Analysis of morphometric measurements and vitreous XO activity revealed significant differences between the PGAtreated groups and the NaCl-treated group (P<0.05). Similarly, apoptotic cell counts in different retinal layers showed that PGA-treated groups had fewer apoptotic cells in all retinal layers than the NaCl-treated ischemic group (P<0.05). PGA may have high protective potential for different retinal layers and cells. Biochemical analysis of vitreous showed that all PGAs decreased vitreous XO activity significantly compared to the NaCl-treated group (P<0.05). However we could not find any statistically significant differences among the analogues. PGAs may reduce the injury induced by I/R, through the inhibition of XO activity, and it seems that their effects are elicited through numerous pathways.

NCX 470 Exerts Retinal Cell Protection and Enhances Ophthalmic Artery Blood Flow After Ischemia/Reperfusion Injury of Optic Nerve Head and Retina

“…Low nanomolar concentrations are essential for maintaining aqueous humor homeostasis, 11 ocular blood flow, 25 and promote rods’ and cones’ activity, 26 whereas excessive NO concentrations (µM – mM), as that produced by inducible nitric oxide synthase (NOS2), have the potential for cytotoxic effects. 27 In our study, NCX 470 diminished ET-1-induced changes in ophthalmic artery resistive index thereby suggesting that an increase in ocular blood flow likely contributed to the beneficial effect of NCX 470 on retina function; however, a bimatoprost-mediated contribution on this phenomenon also seems plausible, as indicated in previous work by Emre and coworkers, 28 where topical dosing of bimatoprost was found to protect rabbit retina from ischemia/reperfusion damage.…”

“…These latter findings are in agreement with previous reports suggesting an anti-apoptotic activity of bimatoprost in cultured RGCs 30 and in vivo following topical dosing in a rabbit model where various prostaglandins, including bimatoprost, were found to reduce apoptotic cell nuclei in retinal layers following ischemia/reperfusion injury. 28 …”

Antioxidant effects of silymarin on ischaemia-reperfusion injuries of the rabbit retina

“…Turgut et al (2008) investigated the antioxidant and protective effects of silymarin on ischaemia and reperfusion injury and reported that animals that were subjected to ischaemiareperfusion exhibited significant increase in serum urea, creatinine, and cystatin C levels compared with the rats treated with silymarin prior to the ischaemia-reperfusion process. Emre et al (2009) compared the protective effects of prostaglandin analogues in the ischaemia and reperfusion model of rabbits eyes and reported that prostaglandin analogues-treated groups had fewer apoptotic cells in all retinal layers than the saline-treated ischaemic group. It has also been reported that prostaglandin analogues decreased vitreous xanthine oxidase activity significantly compared to the saline-treated group.…”

“…After dehydration in acetone, they were embedded in Araldite CY 212. Ultrathin sections were stained with uranyl acetate and lead citrate and examined by a Zeiss Libra 120 transmission electron microscope (Emre et al, 2009). …”

The neuroprotective effect of latanoprost acts via klotho‐mediated suppression of calpain activation after optic nerve transection

“…Latanoprost/LA also exert a neuroprotective effect in the retinal ganglion cells under the ischemia and reperfusion stresses (Emre et al 2009). Several studies have demonstrated that latanoprost/LA protect the RGCs against neuronal degeneration after axonal injury, such as transection or crushing of the optic nerve (Kudo et al 2006;Kanamori et al 2009).…”