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Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts.

ABSTRACT: The paradigm that cataracts are irreversible and that vision from cataracts can only be restored through surgery has recently been challenged by reports that oxysterols such as lanosterol and 25-hydroxycholesterol can restore vision by binding to ?B-crystallin chaperone protein to dissolve or disaggregate lenticular opacities. To confirm this premise, in vitro rat lens studies along with human lens protein solubilization studies were conducted. Cataracts were induced in viable rat lenses cultured for 48?hours in TC-199 bicarbonate media through physical trauma, 10?mM ouabain as Na+/K+ ATPase ion transport inhibitor, or 1?mM of an experimental compound that induces water influx into the lens. Subsequent 48-hour incubation with 15?mM of lanosterol liposomes failed to either reverse these lens opacities or prevent the further progression of cataracts to the nuclear stage. Similarly, 3-day incubation of 47-year old human lenses in media containing 0.20?mM lanosterol or 60-year-old human lenses in 0.25 and 0.50?mM 25-hydroxycholesterol failed to increase the levels of soluble lens proteins or decrease the levels of insoluble lens proteins. These binding studies were followed up with in silico binding studies of lanosterol, 25-hydroxycholesterol, and ATP as a control to two wild type (2WJ7 and 2KLR) and one R120G mutant (2Y1Z) ?B-crystallins using standard MOETM (Molecular Operating Environment) and Schrödinger's Maestro software. Results confirmed that compared to ATP, both oxysterols failed to reach the acceptable threshold binding scores for good predictive binding to the ?B-crystallins. In summary, all three studies failed to provide evidence that lanosterol or 25-hydroxycholesterol have either anti-cataractogenic activity or bind aggregated lens protein to dissolve cataracts.

SUBMITTER: Daszynski DM

PROVIDER: S-EPMC6560215 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts.

Daszynski Damian M DM Santhoshkumar Puttur P Phadte Ashutosh S AS Sharma K Krishna KK Zhong Haizhen A HA Lou Marjorie F MF Kador Peter F PF

Scientific reports 20190611 1

The paradigm that cataracts are irreversible and that vision from cataracts can only be restored through surgery has recently been challenged by reports that oxysterols such as lanosterol and 25-hydroxycholesterol can restore vision by binding to αB-crystallin chaperone protein to dissolve or disaggregate lenticular opacities. To confirm this premise, in vitro rat lens studies along with human lens protein solubilization studies were conducted. Cataracts were induced in viable rat lenses culture ...[more]

PMID: 31186457

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Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts.

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Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts.

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