The Intravitreal Injection of Lanosterol Nanoparticles Rescues Lens Structure Collapse at an Early Stage in Shumiya Cataract Rats

Abstract

We designed an intravitreal injection formulation containing lanosterol nanoparticles (LAN-NPs) via the bead mill method and evaluated the therapeutic effect of LAN-NPs on lens structure collapse and opacification using two rat cataract models (SCR-N, rats with slight lens structure collapse; SCR-C, rats with the combination of a remarkable lens structure collapse and opacification). The particle size of lanosterol in the LAN-NPs was around 50–400 nm. A single injection of LAN-NPs (0.5%) supplied lanosterol into the lens for 48 h, and no irritation or muddiness was observed following repeated injections of LAN-NPs for 6 weeks (once every 2 days). Moreover, LAN-NPs repaired the slight collapse of the lens structure in SCR-N. Although the remarkable changes in the lens structure of SCR-C were not repaired by LAN-NP, the onset of opacification was delayed. In addition, the increase of cataract-related factors (Ca2+ contents, nitric oxide levels, lipid peroxidation and calpain activity levels) in the lenses of SCR-C was attenuated by the repeated injection of LAN-NPs. It is possible that a deficiency of lanosterol promotes the production of oxidative stress. In conclusion, it is difficult to improve serious structural collapse with posterior movement of the lens nucleus with a supplement of lanosterol via LAN-NPs. However, the intravitreal injection of LAN-NPs was found to repair the space and structural collapse in the early stages in the lenses.

Ophthalmic In Situ Gelling System Containing Lanosterol Nanoparticles Delays Collapse of Lens Structure in Shumiya Cataract Rats

“…A greater supplement of Lan content may be needed to reverse crystallin aggregation and restore transparency to opaque lens. Moreover, we previously reported that the serious structural collapses with posterior movement of the lens nucleus were observed in the SCR-C [ 24 ], and the serious structural collapses was not reversed by the instillation of LA-NPs/ISG in this study. Further studies are needed to investigate whether the treatment of Lan can restore opaque lenses to transparency.…”

“…Twenty microliters of samples in methanol were injected, and the Lan in samples was separated by an LC-10AD pump (Shimadzu, Kyoto, Japan) with TSK gel ODS-100S (5 µm, 150 × 2.0 mm I.D., Tosoh Co., Tokyo, Japan), a step gradient experiment was performed using 5% and 100% methanol over 19 min (flow rate of 0.4 mL/min), and the Lan was detected by a Corona Veo detector (Thermo Fisher Scientific, Inc., Waltham, MA, USA). The charger voltage, charger current, and inlet pressure (nitrogen) were 2.66 kV, 0.99 µA, and 61.9 psi, respectively [ 24 ].…”

Identification of differential gene expression pattern in lens epithelial cells derived from cataractous and non-cataractous lenses of Shumiya cataract rat

“…Recently, it has also been reported that lanosterol plays a preventive role in cataract formation, inhibiting lens opacity and reversing crystalline aggregation [18]. Additionally, intravitreal injection of lanosterol nanoparticles has been reported to rescue early stage of lens damage in SCRs [7]. Thus, synthesis of cholesterol by LSS is important to maintain lens transparency.…”

“…It promotes cell apoptosis and senescence and is also associated with many diseases [5,6]. Oxidative stress and reactive oxygen species (ROS) are a major cause of age-related eye diseases, and diets rich in fruits, vegetables, vitamin C, zeaxanthin, lutein, and multivitamin-mineral supplements are recommended for cataracts and age-related macular degeneration (AMD) [7][8][9][10]. Moreover, several risk factors such as advancing age, genetic predisposition, oxidative stress and external and internal factors causing adversely on lens homeostasis have been implicated to contribute to the etiology of cataract formation.…”

“…To understand the molecular mechanism underlying cataract formation, animal models are a prerequisite. Shumiya cataract rats (SCRs) have been used as a model to study congenital cataract, 4 exploring the initiation and development of the disease [7][8][9]. Lens opacity is observed in 66.7% of SCRs [10].…”