Paclitaxel and Urolithin A Prevent Histamine-Induced Neurovascular Breakdown Alike, in an Ex Vivo Rat Eye Model

ACS Chem Neurosci. 2022 Jul 20;13(14):2092-2098. doi: 10.1021/acschemneuro.1c00692. Epub 2022 May 15.

Abstract

Neurovascular eye problems are better prevented than managed or treated. Despite growing concern of occurrence in aging populations and development secondary to diseases such as diabetes and hypertension, we currently have very few options to tackle this global problem. Creating effective and high-throughput screening strategies is as important as the intervention itself. Here, we present for the first time a robust ex vivo rat eye model of histamine-induced vascular damage for investigating the therapeutic potential of paclitaxel (PTX) and urolithin A (UA) as alternatives to dexamethasone for preventing vascular damage in the retina. Extensive loss of vascularization and apoptosis were observed in the histamine-challenged group and successfully prevented in the intervention groups, more significantly in the PTX and UA. These important early results indicate that PTX and UA could be developed as potential preventive strategies for a wide variety of retinal diseases.

Keywords: apoptosis; histamine; paclitaxel; retina; urolithin A; vasculature.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Coumarins / pharmacology
  • Histamine* / pharmacology
  • Paclitaxel* / toxicity
  • Rats

Substances

  • Coumarins
  • 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
  • Histamine
  • Paclitaxel