• COVID-19
  • Biosimilars
  • Cataract Therapeutics
  • DME
  • Gene Therapy
  • Workplace
  • Ptosis
  • Optic Relief
  • Imaging
  • Geographic Atrophy
  • AMD
  • Presbyopia
  • Ocular Surface Disease
  • Practice Management
  • Pediatrics
  • Surgery
  • Therapeutics
  • Optometry
  • Retina
  • Cataract
  • Pharmacy
  • IOL
  • Dry Eye
  • Understanding Antibiotic Resistance
  • Refractive
  • Cornea
  • Glaucoma
  • OCT
  • Ocular Allergy
  • Clinical Diagnosis
  • Technology

HP-B-CD: AMD therapy with cholesterol-lowering capabilities


Investigators set out to determine if treatment crosses blood-retina barrier.

This article was reviewed by Irina A. Pikuleva, PhD

A potential new treatment for age-related macular degeneration (AMD) may be 2-hydropropyl-ß-cyclodextrin (HP-ß-CD), which, evidence suggests, can lower retinal cholesterol.

The earliest manifestation of AMD in the macula is deposition of drusen, cholesterol-rich, pale yellowish formations that can progress to either dry or wet AMD.

The rationale for testing HP-ß-CD was clear.

Related: The state of dry, wet AMD in 2021

Irina A. Pikuleva, PhD, and colleagues have focused their research on cholesterol and off-label use of previously approved products to lower retinal cholesterol.

HP-ß-CD is one such compound, she said, that is shaped like a hollow, truncated cone with a lipophilic inner surface and a hydrophilic outer surface.

This structure allows HP-ß-CD to encapsulate hydrophobic medications and form water-soluble inclusion complexes. HP-ß-CD received FDA approval as a vehicle for drug delivery.

“However, we also know that HP-ß-CD can lower cholesterol in different tissues,” said Pikuleva, professor and vice chairwoman, Department of Ophthalmology and Visual Sciences, director, Visual Sciences Research Center, and Carl F. Asseff Professor of Ophthalmology at Case Western Reserve University in Cleveland, Ohio.

HP-ß-CD has been tested in 2 clinical trials for its off-label cholesterol-lowering capabilities in children with Niemann-Pick disease type C1.

Related: Risk awareness helps identify medication-induced retinal toxicity

Investigation: 4 important points
Pikuleva and colleagues are now testing HP-ß-CD in mice with normal retinal cholesterol and genetically altered mice with increased retinal cholesterol.

The investigators set out to determine whether HP-ß-CD crosses the blood-retina barrier, the best method of HP-ß-CD delivery and the dose, the HP-ß-CD cholesterol-lowering effects, and the mechanism by which cholesterol is lowered.

Feasibility. When the investigators injected the 2 groups of mice with HP-ß-CD—normal HP-ß-CD in the normal mice and HP-ß-CD that fluoresced in the mice with high retinal cholesterol—they found that about 30 minutes after the injections, the HP-ß-CD was seen in the retinal blood vessels in both groups of mice.

Related: Anti-VEGF medications may cause systemic complications in ROP

Two hours after injections, the HP-ß-CD diffused from the retinal blood vessels into the retina; by 8 hours, the HP-ß-CD was washed out of the retina, she reported.

Dosing and effect. The investigators then first tested oral gavage at a dose of 1.6 mg/kg of body weight for delivery of the HP-ß-CD to the retina. They measured the retinal cholesterol in both mice groups. They saw that, even with normal cholesterol, the cholesterol level could be reduced by HP-ß-CD.

They also evaluated the effect of increasing subcutaneous doses of HP-ß-CD for twice a week and 3 times a week for 29 days or 14 days, respectively.

“Even with this delivery route, we saw a decrease in the retinal cholesterol in treated vessels. But when we compared the extent of the cholesterol decrease, we found it to be smaller than that achieved with oral gavage,” Pikuleva said.

Related: Research is unfolding the proteins in retinitis pigmentosa

Mechanism. The investigators, who published their findings in the British Journal of Pharmacology,1 tested the expression of several cholesterol-related genes and they measured the protein levels in the retina.

They found that in both animal models the evidence indicated that HP-ß-CD is taken up by the cells, combined with cholesterol, and effluxed from the cells. HP-ß-CD also can extract cholesterol from the plasma membranes that form the cell surface.

“Based on our studies, HP-ß-CD should be further considered as a potential therapeutic for AMD,” Pikuleva concluded.

Read more by Lynda Charters


Irina A. Pikuleva, PhD
Pikuleva’s funding resources include National Institutes of Health grants EY025383, EY018383, and EY011373 and the unrestricted grant from the Cleveland Eye Bank Foundation. Pikuleva is a Carl F. Asseff Professor of Ophthalmology.


1. El-Darzi N, Mast N, Petrov AM, Pikuleva IA. 2-Hydroxypropyl-β-cyclodextrin reduces retinal cholesterol in wild-type and Cyp27a1-/-Cyp46a1-/- mice with deficiency in the oxysterol production. Br J Pharmacol. Published online July 22, 2020. doi:10.1111/bph.15209

Related Videos
EyeCon 2024: Peter J. McDonnell, MD, marvels on mentoring, modern technology, and ophthalmology’s future
EyeCon Co-chair Oluwatosin U. Smith, MD: Passion for Research and Education Drives Her Commitment to Ophthalmology
Video 3 - "Approaching Asymptomatic Cases with Risk Factors"
Video 2 - "Do Dry Eye Diagnostics Change the Management of Dry Eye?"
Dr. SriniVas Sadda Discusses Vision for ARVO as New President: Collaboration, Funding Challenges, and Impact of Annual Meetings
Deb Ristvedt, DO's CIME 2024 Talk Highlights Innovations in Treating Glaucoma via the Trabecular Meshwork
Dr. Inder Paul Singh's Insights: Improving Glaucoma Outcomes with Early Intervention and Reduced Medication
CIME 2024: Kelsey Roelofs, MD, details collaborative strategies for the management of thyroid eye disease
CIME 2024: Diagnostic tips and treatments for managing Demodex blepharitis
© 2024 MJH Life Sciences

All rights reserved.