Air Pollution and Glaucoma

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Article initiated by:
Abdelrahman M. Elhusseiny, MD, MSc, DYLAN.FREEMAN, Dan Arreaza-Kaufman
All contributors:
Ahmad A. Aref, MD, MBA, Ahmad A. Aref, MD, MBA, Daniel B. Moore, MD, Abdelrahman M. Elhusseiny, MD, MSc
Assigned editor:
Arsham Sheybani, MD
Review:
Assigned status Update Pending
 by Ahmad A. Aref, MD, MBA on July 10, 2023.


Background

Air pollution is a significant global health concern linked to various diseases, including cardiopulmonary disease, neurologic disease, and cancer.[1] [2][3] The primary drivers of air pollution are fossil fuel combustion, motor vehicles, industrial facilities, and forest fires.[4] Despite air quality standards, harmful levels of pollutants, including PM2.5 (particulate matter <2.5 μm in diameter), continue to impact both developing and industrialized countries. Nearly the entire global population breathes air that exceeds WHO guideline limits, with low and middle-income countries experiencing the highest exposures.[5] PM2.5, which can penetrate into the lungs and bloodstream, is associated with respiratory diseases and systemic conditions such as coronary artery disease, diabetes mellitus, chronic kidney disease, and preterm birth.[6][7][8] [9] Recent research suggests a link between air pollution, PM2.5, and ocular pathologies, including dry eye, cataract, uveitis, age-related macular degeneration (AMD), and glaucoma.[10][11][12][13]

Glaucoma is a leading cause of blindness globally, and its prevalence is higher in urban areas, raising suspicions of a potential association with air pollution.[14] The exact mechanisms of glaucoma development remain unclear, but oxidative stress, inflammatory pathways, and microvascular changes have been implicated in the diseases caused by air pollution. It is hypothesized that PM2.5 accumulates in the lungs, activating inflammation and releasing inflammatory mediators. PM2.5 can also enter the bloodstream, causing systemic immune-mediated inflammation, oxidative stress, cellular dysfunction, and apoptosis.[15][16]

Proposed Hypotheses

Evidence suggests that PM2.5 can translocate across the pulmonary epithelium, entering the bloodstream and causing systemic immune-mediated inflammation and oxidative stress. This, in turn, leads to cellular dysfunction and apoptosis.[16] Regarding ocular tissue and glaucoma, Chua et al. demonstrated that higher PM2.5 is associated with a thinner ganglion cell-inner plexiform layer complex. The proposed mechanism involves toxicity to ocular tissues mediated by NO, IL-8, and NLRP3, causing oxidative stress and pyroptosis in trabecular meshwork cells.[17]

In addition, Li et al. conducted a study in which mouse eyes and human trabecular meshwork cells were exposed to topical PM2.5. Cell viability, NLRP3/caspase-1 IL 1B, GSDMD expression, ROS production, and cell contractility were measured. The authors demonstrated an upregulation of the NLRP3 inflammasome, caspase-1, IL-1β, GSDMD protein levels, and elevated reactive oxygen species. This suggests that PM2.5 has a direct toxic effect on intraocular tissues mediated by oxidative stress and subsequent NLRP3 inflammasome-mediated pyroptosis in trabecular meshwork cells.[18] These proposed ocular mechanisms align with the existing research and inflammatory pathways implicated in PM2.5 toxic effects on other organ systems, including the heart, lungs, kidneys, and nervous system.

Effect on Intraocular Pressure

The impact of PM2.5 on intraocular pressure (IOP) remains unclear. In a study by Chua et al., PM2.5 was found to be associated with a thinner macular ganglion cell-inner plexiform layer, as measured by spectral domain optical coherence tomography.[17] However, no clinically relevant relationship between PM2.5 and IOP was demonstrated, suggesting potential direct neurotoxic or vascular effects.[17] While IOP is a significant risk factor for primary open-angle glaucoma (POAG), a considerable proportion of glaucoma patients present with normal-range IOP, indicating the involvement of pressure-independent mechanisms in glaucoma progression. These mechanisms may include oxidative stress and inflammatory pathways.

Most reviewed studies did not find a significant association between PM2.5 and IOP, suggesting the involvement of pressure-independent mechanisms. However, a study by Yang et al. reported a significant but weak relationship between long-term PM2.5 exposure and IOP in a large Chinese population.[19] This finding is further supported by data from the U.K. Biobank study, which linked PM2.5 exposure to mildly elevated IOP.[17] While these studies suggest a potential link between PM2.5 and IOP, further research is needed to elucidate the underlying mechanisms and establish a clearer understanding of the relationship between air pollution and IOP in the context of glaucoma.

Relevant studies

In our search on May 2023, we found a total of 14 studies evaluating the relationship between PM2.5 and glaucoma. These studies demonstrated a consistent association between PM2.5 and glaucoma. Wang et al. found glaucoma to be associated with lower socioeconomic level, older age, female gender, higher U.V. radiation, and air pollution, specifically PM2.5.[20] In 2021, Sun et al. investigated the relationship between PM2.5 and POAG in the Taiwanese population over five years. The study population was categorized into four groups based on WHO PM2.5 exposure standards and found increasing rates of POAG in each quartile (OR per level 1.193).[21] Another large study of over 9,000 infants conducted by Min et al. found an association between PM10 and childhood glaucoma. The research team similarly categorized the participants into quartiles based on exposure and found that the probability of childhood glaucoma increased with increasing PM10 quartiles.[22] Particulate matter is also associated with an increased incidence of acute glaucoma, according to Li et al.[23] Chiang et al. found a similar link between PM2.5 exposure and glaucoma in patients with diabetes (Odds ratio (OR) 1.7 between Q4 and Q1, 95% CI: 1.084-2.764)[24], and Grant et al. conducted a Canadian multicenter longitudinal study of over 30,000 adults, finding PM2.5 to be associated with glaucoma (OR 1.14, CI 1.01-1.29).[25]

Conclusion

In conclusion, recent studies provide compelling evidence of a statistically significant link between PM2.5 and glaucoma. This association is likely mediated by a pressure-independent mechanism involving direct toxicity to ocular tissue caused by inflammatory mediators. The accumulation of PM2.5 in the alveoli and its subsequent impact on trabecular meshwork cells and the ganglion cell-inner plexiform layer have been implicated in glaucoma pathogenesis. These findings align with the well-established role of air pollution in inducing inflammation and oxidative stress in various organ systems.

However, the relationship between air pollution and IOP remains unclear, with some studies reporting modest increases in IOP while others finding no significant change. Further research is needed to investigate the complex interplay between air pollution, particulate matter, and IOP regulation in the context of glaucoma.

Considering the widespread impact of air pollution on billions of individuals worldwide, deepening our understanding of how particulate matter affects ocular health is imperative. More studies are needed to comprehensively evaluate the role of air pollution, specifically PM2.5, in the development and progression of glaucoma.

  1. ↑ Hayes RB, Lim C, Zhang Y, Cromar K, Shao Y, Reynolds HR, Silverman DT, Jones RR, Park Y, Jerrett M, Ahn J, Thurston GD. PM2.5 air pollution and cause-specific cardiovascular disease mortality. Int J Epidemiol. 2020 Feb 1;49(1):25-35.
  2. ↑ Hahad O, Lelieveld J, Birklein F, Lieb K, Daiber A, Münzel T. Ambient Air Pollution Increases the Risk of Cerebrovascular and Neuropsychiatric Disorders through Induction of Inflammation and Oxidative Stress. Int J Mol Sci. 2020 Jun 17;21(12):4306.
  3. ↑ Schraufnagel DE, Balmes JR, Cowl CT, De Matteis S, Jung SH, Mortimer K, Perez-Padilla R, Rice MB, Riojas-Rodriguez H, Sood A, Thurston GD, To T, Vanker A, Wuebbles DJ. Air Pollution and Noncommunicable Diseases: A Review by the Forum of International Respiratory Societies' Environmental Committee, Part 2: Air Pollution and Organ Systems. Chest. 2019 Feb;155(2):417-426.
  4. ↑ Perera F. Pollution from Fossil-Fuel Combustion is the Leading Environmental Threat to Global Pediatric Health and Equity: Solutions Exist. Int J Environ Res Public Health. 2017 Dec 23;15(1):16.
  5. ↑ “Billions of People Still Breathe Unhealthy Air: New Who Data.” World Health Organization, 4 Apr. 2022
  6. ↑ Bekkar B, Pacheco S, Basu R, DeNicola N. Association of Air Pollution and Heat Exposure With Preterm Birth, Low Birth Weight, and Stillbirth in the U.S.: A Systematic Review. JAMA Netw Open. 2020 Jun 1;3(6):e208243.
  7. ↑ Kaufman JD, Adar SD, Barr RG, Budoff M, Burke GL, Curl CL, Daviglus ML, Diez Roux AV, Gassett AJ, Jacobs DR Jr, Kronmal R, Larson TV, Navas-Acien A, Olives C, Sampson PD, Sheppard L, Siscovick DS, Stein JH, Szpiro AA, Watson KE. Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution): a longitudinal cohort study. Lancet. 2016 Aug 13;388(10045):696-704
  8. ↑ Liang Z, Wang W, Wang Y, Ma L, Liang C, Li P, Yang C, Wei F, Li S, Zhang L. Urbanization, ambient air pollution, and prevalence of chronic kidney disease: A nationwide cross-sectional study. Environ Int. 2021 Nov;156:106752.
  9. ↑ Liang Z, Wang W, Wang Y, Ma L, Liang C, Li P, Yang C, Wei F, Li S, Zhang L. Urbanization, ambient air pollution, and prevalence of chronic kidney disease: A nationwide cross-sectional study. Environ Int. 2021 Nov;156:106752.
  10. ↑ Kim Y, Choi YH, Kim MK, Paik HJ, Kim DH. Different adverse effects of air pollutants on dry eye disease: Ozone, PM(2.5), and PM(10). Environ Pollut. Oct 2020;265(Pt B):115039.
  11. ↑ Tan H, Pan S, Zhong Z, Su G, Kijlstra A, Yang P. Association between Fine Particulate Air Pollution and the Onset of Uveitis in Mainland China. Ocul Immunol Inflamm. 2022 Oct-Nov;30(7-8):1810-1815.
  12. ↑ Chua SYL, Khawaja AP, Desai P, et al. The Association of Ambient Air Pollution With Cataract Surgery in U.K. Biobank Participants: Prospective Cohort Study. Invest Ophthalmol Vis Sci. 12 01 2021;62(15):7.
  13. ↑ Ju MJ, Kim J, Park SK, Kim DH, Choi YH. Long-term exposure to ambient air pollutants and age-related macular degeneration in middle-aged and older adults. Environ Res. 03 2022;204(Pt A):111953.
  14. ↑ Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014 Nov;121(11):2081-90.
  15. ↑ Thangavel P, Park D, Lee YC. Recent Insights into Particulate Matter (PM2.5)-Mediated Toxicity in Humans: An Overview. Int J Environ Res Public Health. 2022 Jun 19;19(12):7511
  16. ↑ 16.0 16.1 Fiordelisi, A.; Piscitelli, P.; Trimarco, B.; Coscioni, E.; Iaccarino, G.; Sorriento, D. The mechanisms of air pollution and particulate matter in cardiovascular diseases. Heart Fail. Rev. 2017, 22, 337–347.
  17. ↑ 17.0 17.1 17.2 17.3 Chua, S.Y.L.; Khawaja, A.P.; Morgan, J.; Strouthidis, N.; Reisman, C.; Dick, A.D.; Khaw, P.T.; Patel, P.J.; Foster, P.J. The Relationship Between Ambient Atmospheric Fine Particulate Matter (PM2.5) and Glaucoma in a Large Community Cohort. Invest Ophthalmol. Vis. Sci. 2019, 60, 4915–4923
  18. ↑ Li L, Xing C, Zhou J et al (2021) Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis. Part Fibre Toxicol 18:1–13.
  19. ↑ Yang X, Yang Z, Liu Y, et al. The association between long-term exposure to ambient fine particulate matter and glaucoma: a nation-wide epidemiological study among Chinese adults. Int J Hyg Environ Health. 2021; 238: 113858.
  20. ↑ Wang, W.; He, M.; Li, Z.; Huang, W. Epidemiological variations and trends in health burden of glaucoma worldwide. Acta Ophthalmol. 2019, 97, e349–e355.
  21. ↑ Sun, H.Y.; Luo, C.W.; Chiang, Y.W.; Yeh, K.L.; Li, Y.C.; Ho, Y.C.; Lee, S.S.; Chen, W.Y.; Chen, C.J.; Kuan, Y.H. Association Between PM2.5 Exposure Level and Primary Open-Angle Glaucoma in Taiwanese Adults: A Nested Case-Control Study. Int. J. Environ. Res. Public Health 2021, 18, 1714.
  22. ↑ Min, K.B.; Min, J.Y. Association of Ambient Particulate Matter Exposure with the Incidence of Glaucoma in Childhood. Am. J. Ophthalmol. 2020, 211, 176–182.
  23. ↑ Li L, Zhu Y, Han B, Chen R, Man X, Sun X, Kan H, Lei Y. Acute exposure to air pollutants increase the risk of acute glaucoma. BMC Public Health. 2022 Sep 20;22(1):1782.
  24. ↑ Chiang YW, Wu SW, Luo CW et al (2021) Air pollutant particles, PM2.5, exposure and glaucoma in patients with diabetes: a national population-based nested case–control study. Int J Environ Res Public Health 18.
  25. ↑ Grant A, Leung G, Aubin MJ, Kergoat MJ, Li G, Freeman EE. Fine particulate matter and age-related eye disease: the Canadian longitudinal study on aging. Investig Ophthalmol Vis Sci. 2021; 62(10): 7.
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