Lanosterol Synthase Pathway Alleviates Lens Opacity in Age-Related Cortical Cataract.

Huaijin Guan,Bai Qin,Yuanyuan Tu,Mei Yang,Lele Li,Lihua Kang,Xinyue Shen,Manhui Zhu,Rutan Zhang

doi:10.1155/2018/4125893

Huaijin Guan, Bai Qin + Show 7 more

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https://doi.org/10.1155/2018/4125893

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Abstract

Purpose Lanosterol synthase (LSS) abnormity contributes to lens opacity in rats, mice, dogs, and human congenital cataract development. This study examined whether LSS pathway has a role in different subtypes of age-related cataract (ARC). Methods A total of 390 patients with ARC and 88 age-matched non-ARC patients were enrolled in this study. LSS expression was analyzed by western blot and enzyme-linked immunosorbent assay (ELISA). To further examine the function of LSS, we used U18666A, an LSS inhibitor in rat lens culture system. Results In lens epithelial cells (LECs), LSS expression in LECs increased with opaque degree C II, while it decreased with opaque degree C IV and C V. While in the cortex of age-related cortical cataract (ARCC), LSS expression was negatively related to opaque degree, while lanosterol level was positively correlated to opaque degree. No obvious change in both LSS and lanosterol level was found in either LECs or the cortex of age-related nuclear cataract (ARNC) and age-related posterior subcapsular cataract (ARPSC). In vitro, inhibiting LSS activity induced rat lens opacity and lanosterol effectively delayed the occurrence of lens opacity. Conclusions This study indicated that LSS and lanosterol were localized in the lens of human ARC, including ARCC, ARNC, and ARPSC. LSS and lanosterol level are only correlated with opaque degree of ARCC. Furthermore, activated LSS pathway in lens is protective for lens transparency in cortical cataract.

Highlights

Cataract is one of the leading causes of blindness worldwide and cataract is the major cause of blindness in developing countries, including China [1, 2]. e clinical characteristic of cataract is lenticular opacity and the final visual impairment
Human lens samples including lens capsules and the cortex were obtained from Department of Ophthalmology, Afliated Hospital of Nantong University. e lens tissues from 390 patients with di erent subtypes of Age-related cataract (ARC) during phacoemulsi cation were collected. e clinical diagnosis of ARC is based on criteria of the Lens Opacities Classication System II (LOCS II) [20]
While in the cortex of human age-related cortical cataract (ARCC), Lanosterol synthase (LSS) decreased with the aggravation of opaque degree (Figures 1(a) and 1(b))

Summary

Introduction

Cataract is one of the leading causes of blindness worldwide and cataract is the major cause of blindness in developing countries, including China [1, 2]. e clinical characteristic of cataract is lenticular opacity and the final visual impairment. Age-related cataract (ARC) is the most common type [3, 4]. Preventing or delaying the onset of cataracts by pharmacological interventions has been an attractive field of research in ophthalmology [7, 8]. Studies have identified multiple risk factors related to cataract formation, including genetic predisposition, aging, oxidative stress, ultraviolet (UV) light, systematic diseases, and toxic agents [9, 10]. Especially cholesterol metabolic disturbance, have been proposed to be a potential factor for cataract. Whether cholesterol is a risk or protective factor in cataract remains in debate [11,12,13]. Researchers demonstrate that lanosterol, not cholesterol, plays a preventive role in cataract formation, inhibiting lens opacity, and reversing crystalline aggregation [14]

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