Cytoprotective Effect of Astaxanthin in a Model of Normal Intraocular Pressure Glaucoma.

Kasumi Kikuchi,Kosuke Noda,Susumu Ishida,Atsuhiro Kanda,Zhenyu Dong,Miyuki Murata,Yasuhiro Shinmei,Takayuki Harada

doi:10.1155/2020/9539681

Abstract

Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies. Lowering intraocular pressure is currently the only way to treat glaucoma, but it is often insufficient to inhibit the progression of the disease. Glaucoma is a multifactorial disease, and the involvement of oxidative stress has recently received much attention. In the present study, we investigated the cytoprotective effect of astaxanthin (AST) on RGC degeneration using a normal-tension glaucoma (NTG) mouse model, which lacks the glutamate/aspartate transporter (Glast) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure. Three-week-old Glast± mice were given intraperitoneal injections of AST at 10, 30, or 60 mg/kg/day or vehicle alone, and littermate control mice were given vehicle alone for 14 days, respectively. Five weeks after birth, the number of RGCs was counted in paraffin sections of retinal tissues stained with hematoxylin and eosin. We also used a retrograde labeling technique to quantify the number of RGCs. Additionally, the phosphorylated (p) IκB/total IκB ratio and the 4-hydroxynonenal (HNE) were measured in retinal tissues. The number of RGCs in Glast± mice was significantly decreased compared with that in control mice. RGC loss was suppressed by the administration of AST at 60 mg/kg/day, compared with vehicle alone. Following AST administration, the concentration of 4-HNE in the retina was also suppressed, but the pIκB/IκB ratio did not change. Our study revealed that the antioxidative stress effects of AST inhibit RGC degeneration in the retina and may be useful in the treatment of NTG.

Highlights

Glaucoma is one of the leading causes of blindness worldwide [1, 2], characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies
Glaucoma is associated with chronic elevation of intraocular pressure (IOP), and lowering IOP is associated with an attenuation of progressive optic nerve damage [3,4,5]. e main goal in glaucoma therapy is controlling IOP to a target level by medical therapy and parasurgical and surgical approaches in order to prevent or stop the loss of visual field [6]
A growing body of evidence has demonstrated that IOP reduction alone is not sufficient to inhibit the progression of the disease [7], which suggests the contribution of other factors in the pathogenesis of glaucoma

Summary

Introduction

Glaucoma is one of the leading causes of blindness worldwide [1, 2], characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies. Astaxanthin (AST) is a naturally occurring carotenoid whose structural and functional characteristics make it a promising bioactive compound for the prevention of several human diseases, as well as the maintenance of good health [14]. It belongs to the family of xanthophylls and is especially common in marine environments where it can be observed as a red-colored pigment that contributes to the pinkish-red color of salmonids, shrimps, lobsters, and crayfish’s flesh [15]. We investigated the cytoprotective effect of AST on RGC loss using Glast heterozygous knockout (Glast±) mice

Materials and Methods

Results

AST-Mediated Protection of RGCs Detected by Retrograde

Discussion