Inhibitory effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system

Keke Zhang; Wenwen He; Yu Du; Yugui Zhou; Xiaokang Wu; Jie Zhu; Xiangjia Zhu; Kang Zhang; Yi Lu

doi:10.1093/pcmedi/pbac021

Inhibitory effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system

Precis Clin Med. 2022 Aug 24;5(3):pbac021. doi: 10.1093/pcmedi/pbac021. eCollection 2022 Sep.

Authors

Keke Zhang^{1

2

3

4}, Wenwen He^{1

2

3

4}, Yu Du^{1

2

3

4}, Yugui Zhou^{5

6}, Xiaokang Wu⁷, Jie Zhu^{5

8}, Xiangjia Zhu^{1

2

3

4}, Kang Zhang⁹, Yi Lu^{1

2

3

4}

Affiliations

¹ Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
² Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
³ NHC Key Laboratory of Myopia (Fudan University), Shanghai 200031, China.
⁴ Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai 200031, China.
⁵ Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510620, China.
⁶ Institute for Genomic Medicine, Institute of Engineering in Medicine, and Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA.
⁷ Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA 90048, USA.
⁸ Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510440, China.
⁹ Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau 999078, China.

Abstract

Background: To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.

Methods: Nine elder cynomolgus monkeys were used, consisting of three monkeys without cataract as controls, three monkeys with naturally occurring cortical cataract, and three monkeys with nuclear cataract as intervention groups. Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract. Fluorescence changes of injected thermogel and cataract progression were observed. Lanosterol concentration in aqueous humor, solubility changes in lens proteins, and oxidative stress levels were analyzed in the lenses of the control and intervention groups.

Results: Injected thermogel showed decreased fluorescence during follow up. Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased, which was in accordance with the changes in cortical lens clarity. However, lenses with nuclear opacification showed little change. In the cortical region of lenses with cortical cataract, solubility of α-crystallin was significantly increased after administration of lanosterol, as well as the reduction of oxidative stress.

Conclusions: We demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates. Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages, possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status. Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment.

Keywords: cataract; drug release; lanosterol; lens; monkeys.