Cholesterol homeostasis is essential in normal physiology of all cells One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT) In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression

https://www.mdpi.com/1422-0067/22/4/1593/pdf

The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM2.5 on intraocular pressure (IOP). To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1β, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM2.5-induced damages. The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1β. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM2.5 induced adverse effects. This study ﻿provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.

/pdf/airborne-particulate-matter-pm-2-5-triggers-ocular-9rc2b425pd.pdf

Airborne particulate matter (PM 2.5 ) triggers ocular hypertension and glaucoma through pyroptosis.

Air pollution is inevitably the result of human civilization, industrialization, and globalization. It is composed of a mixture of gases and particles at harmful levels. Particulate matter (PM), nitrogen oxides (NOx), and carbon dioxides (CO2) are mainly generated from vehicle emissions and fuel consumption and are the main materials causing outdoor air pollution. Exposure to polluted outdoor air has been proven to be harmful to human eyes. On the other hand, indoor air pollution from environmental tobacco smoking, heating, cooking, or poor indoor ventilation is also related to several eye diseases, including conjunctivitis, glaucoma, cataracts, and age-related macular degeneration (AMD). In the past 30 years, no updated review has provided an overview of the impact of air pollution on the eye. We reviewed reports on air pollution and eye diseases in the last three decades in the PubMed database, Medline databases, and Google Scholar and discussed the effect of various outdoor and indoor pollutants on human eyes.

/pdf/the-adverse-effects-of-air-pollution-on-the-eye-a-review-2ex8w4w7.pdf

The Adverse Effects of Air Pollution on the Eye: A Review

OBJECTIVE\nExposure to particulate matter less than 2.5 μm in diameter (PM2.5) is associated with asthma and respiratory symptoms, but little is known about the influence of PM2.5 on allergic conjunctivitis. The purpose of this study was to examine the association of PM2.5 with outpatient attendance for allergic conjunctivitis.\n\n\nMETHODS\nWe conducted a time-series analysis of the association between outpatient attendance for allergic conjunctivitis and PM2.5 levels from May to July (non-pollen season) and from August to October (the autumnal pollen season) in 2012. Air pollution data (including the levels of PM2.5, oxidants, nitric oxide, nitrogen dioxide, nitrogen oxide, carbon monoxide, methane, non-methane hydrocarbons, and total hydrocarbons) and data on the daily weather conditions (temperature, wind speed, and humidity) were collected at a centrally located monitoring station in Tokyo. We calculated weekly average values for the daily number of outpatient visits, as well as the air pollution and weather data, and used the weekly average values for analysis.\n\n\nRESULTS\nThere was a significant association between the number of outpatient visits for allergic conjunctivitis and the PM2.5 level (r=0.62, p=0.0177) from May to July, while no correlation was found between the number of outpatient visits and any variable assessed from August to November. Multivariate analysis also showed that PM2.5 was a significant predictor of the number of outpatient visits from May to July (odds ratio=9.05, p=0.0463), while there were no significant predictors of the number of outpatient visits from August to October. From May to July, PM2.5 showed a negative correlation with humidity (r=-0.53, p=0.0499).\n\n\nCONCLUSIONS\nThese findings suggest a possible role of PM2.5 in the development of allergic conjunctivitis during the non-pollen season. This association between PM2.5 and allergic conjunctivitis may have broad public health implications in relation to allergic diseases.

Airborne Particulate Matter (PM2.5) and Prevalence of Allergic Conjunctivitis in Japan

Tumor necrosis factor-alpha and interferon-gamma induce inflammasome-mediated corneal endothelial cell death.

Airborne particulate matter (PM2.5) triggers cornea inflammation and pyroptosis via NLRP3 activation

Purpose This study aimed to investigate the role and pathophysiological mechanism of ATP binding cassette transporter A1 (ABCA1) in regulating the IOP and aqueous humor outflow. Methods ABCA1 expression was measured in trabecular meshwork samples obtained from patients with POAG and human donor eyes by Western blot. To further evaluate the functional significance of ABCA1, porcine angular aqueous plexus (AAP) cells, which are equivalent to human Schlemm's canal endothelial cells, were either treated with ABCA1 agonist GW3965 or transduced with lentivirus expressing ABCA1-shRNA. Transendothelial electrical resistance, protein expression, and nitric oxide (NO) concentration were measured. GW3965 was administered by intracameral injection. IOP and aqueous humor outflow facility were also measured. Results ABCA1 expression was significantly higher in the trabecular meshwork tissue of patients with POAG compared with controls. ABCA1 upregulation in angular aqueous plexus cells decreased the transendothelial electrical resistance in the angular aqueous plexus monolayers accompanied by a 0.56-fold decrease in caveolin-1 expression and a 2.85-fold and 1.17-fold increase in endothelial NO synthase expression and NO concentration, respectively (n = 3, P < 0.05). Conversely, ABCA1 downregulation increased transendothelial electrical resistance and caveolin-1 expression and decreased endothelial NO synthase expression and NO production (n = 3, P < 0.05). GW3965 decreased IOP and significantly increased conventional outflow facility (P < 0.05). Conclusions Regulation of aqueous humor outflow via the caveolin-1/endothelial NO synthase/NO pathway is a newly defined function of ABCA1 that is different from its traditional role in mediating cholesterol efflux. ABCA1 is a compelling, novel therapeutic candidate for the treatment of glaucoma and ocular hypertension.

Liangliang Niu

Papers

Airborne particulate matter (PM2.5) triggers cornea inflammation and pyroptosis via NLRP3 activation

Airborne particulate matter (PM 2.5 ) triggers ocular hypertension and glaucoma through pyroptosis.

ABCA1 Regulates IOP by Modulating Cav1/eNOS/NO Signaling Pathway.

Endogenous dual stimuli-activated NO generation in the conventional outflow pathway for precision glaucoma therapy.

Lifetime exposure of ambient PM2.5 elevates intraocular pressure in young mice.