Neuroprotective effects of lutein in a rat model of retinal detachment

Abstract

BackgroundRetinal detachment (RD) is a leading cause of blindness, and although final surgical re-attachment rate has greatly improved, visual outcome in many macula-off detachments is disappointing, mainly because of photoreceptor cell death. We previously showed that lutein is anti-apoptotic in rodent models of ischemia/reperfusion injury. The objective of this study is to investigate lutein as a possible pharmacological adjunct to surgery.MethodsSubretinal injections of 1.4 % sodium hyaluronate were used to induce RD in Sprague–Dawley rats until their retinae were approximately 70 % detached. Daily injections of corn oil (control group) or 0.5 mg/kg lutein in corn oil (treatment group) were given intraperitoneally starting 4 h after RD induction. Animals were euthanized 3 days and 30 days after RD and their retinae were analyzed for photoreceptor apoptosis and cell survival at the outer nuclear layer (ONL) using TUNEL staining and cell counting on retinal sections. Glial fibrillary acidic protein (GFAP) and rhodopsin (RHO) expression were evaluated with immunohistochemistry. Western blotting was done with antibodies against cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9 to delineate lutein’s mechanism of action in the apoptotic cascade. To seek a possible therapeutic time window, the same set of experiments was repeated with treatment commencing 36 h after RD.ResultsWhen lutein was given 4 h after RD, there were significantly fewer TUNEL-positive cells in ONL 3 days after RD when compared with the vehicle group. Cell counting showed that there were significantly more nuclei in ONL in lutein-treated retinae by day 30. Treatment groups also showed significantly reduced GFAP immunoreactivity and preserved RHO expression. At day 3 after RD, Western blotting showed reduced expression of cleaved caspase-3 and cleaved caspase-8 in the treatment group. No difference was found for cleaved caspase-9. When lutein was given 36 h after RD similar results were observed.ConclusionsOur results suggest that lutein is a potent neuroprotective agent that can salvage photoreceptors in rats with RD, with a therapeutic window of at least 36 h. The use of lutein in patients with RD may serve as an adjunct to surgery to improve visual outcomes.

Lutein Attenuates Both Apoptosis and Autophagy upon Cobalt (II) Chloride-Induced Hypoxia in Rat Műller Cells

“…In the present study, we showed that treatment of 20μM of lutein also enhanced Bcl-2 protein expression and abrogated Bax/Bcl-2 ratio after 24 hours of hypoxic injury. More importantly, lutein attenuated cleavage of caspase 3, consistent with our previous finding using an animal model of retinal detachment [36], further strengthening the notion that lutein mediated cytoprotection through regulating the cascade of caspase-associated pathway.…”

Lutein Has a Protective Effect on Hepatotoxicity Induced by Arsenic via Nrf2 Signaling

“…To the best of our knowledge, there have been no reports on the effects of lutein on neurons in the brain in a rodent stroke model [27]. In the present study, we found significant interactions between LU and ATO treatments on body weight, liver index, ALT, AST, T-AOC levels, GSH, and MDA contents.…”

Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences

“…These studies involve neuroprotection and controlling reactive gliosis, one of the major intraretinal changes in PVR. Agents such as melatonin (Iribarne et al, 2007), aspirin (Bazan et al, 2010), tauroursodeoxycholic acid (TUDCA) (Fernandez-Sanchez et al, 2011;Mantopoulos et al, 2011), lutein (Woo et al, 2013), and especially anti-TNF-a (Nakazawa et al, 2011) may provide new therapeutic neuroprotective avenues to treat photoreceptor degeneration after a RD. They may also interfere at the same time with the glial processes that occur after an ischemic event in the retina (Fernandez-Bueno et al, 2013a), much like that which occurs in the CNS (Alonso- Alconada et al, 2013;Bae et al, 2006).…”