Abstract
Purpose :
To prepare an APOE KO-DBA/2J hybrid mouse of pigment dispersion glaucoma (PDG) and assess whether cholesterol metabolism interacts with intraocular pressure (IOP) regulation in glaucoma.
Methods :
Three experiments were conducted: (A). We bred 10 generations of DBA/2J and APOE KO to derive hybrid mice. Mice were subjected to anterior segment imaging on a microscope. IOP measurement was performed using Tonolab. We subjected 6 mice each to Atorvastatin or Ezetimibe intravenous injections daily while both groups were on travoprost (Travatan,Novartis) for 5 days. (B). In a different study design, 18 mice were subjected to cholesterol lowering using Atorvastatin for 10 days. On day 11 they were divided into 3 groups: Atorvastatin, Atorvastatin+ Ezetimibe or just Ezetimibe (n= 6 each). All were on travoprost daily eye drops throughout the study period. All mouse experimental data (equal distribution of males and females) were subjected to t-test and findings were significant with respect to control group. (C). As a separate analysis, using data from the SOURCE repository, we reviewed the IOPs of patients with open angle glaucoma and hyperlipidemia before vs after starting treatment with a statin (n=7825) versus others already taking statins, before vs after starting Ezetimibe (n=295). The gender and race of the patients were recorded. Comparisons of changes to IOP were done using Pearson’s Chi-square and Wilcoxcon rank sum tests.
Results :
(A). The mice subjected to Atorvastatin with similar treatment with glaucoma drops showed 4-6 mm of Hg lower IOP compared to the mice given Ezetimibe alone. (B). Mice given Atorvastatin for 10 days were then subjected to Atrovastatin alone, Ezetimibe alone, or Atorvastatin + Ezetimibe. At day 10, the mean IOP was 18.2 mmHg OD and 18.4mmHg OS. Those then given Atorvastatin only showed an average IOP of 18.6 mm Hg while Atorvastatin + Ezetimibe showed IOPs of 20.8 ( mm Hg, respectively, Ezetimibe alone showed 23.0-mm Hg respectively. (C). In our analyses of human data from SOURCE, the mean IOP OD changed from 16.2 mmHg prior to starting statins to 15.6 mmHg afterwards. By comparison, among patients with glaucoma already on statins, the mean IOP OD changed from 15.8 mmHg prior to starting Ezetimibe to 15.2 mmHg afterwards. (p≤0.002).
Conclusions :
Our analysis of mouse and human data is consistent with the hypothesis that the cholesterol metabolism interfers with pigment dispersion glaucoma.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.