Dry eye and macular degeneration: A convergence of aging, inflammation, and telomere biology

Dry eye disease (DED) and age-related macular degeneration (AMD) are among the most common ocular disorders associated with aging, affecting the ocular surface and the retina, respectively. Although clinically distinct, both conditions share underlying biological processes driven by aging, including oxidative stress, chronic low-grade inflammation, mitochondrial dysfunction, and cellular senescence. Increasingly, telomere biology—particularly telomere shortening and telomere-associated DNA damage—is being examined as a unifying mechanism that may link ocular aging to dysfunction across different tissues, including those involved in tear production as well as photoreceptor and retinal pigment epithelium (RPE) health.

Oxidative stress and inflammation: Shared culprits

The accumulation of reactive oxygen species (ROS) across ocular tissues not only directly damages nucleic acids, proteins, and lipids but also functions as an upstream driver of inflammation and tear hyperosmolarity, collectively disrupting cellular homeostasis.¹ The protective antioxidant defenses of the tear film—such as lactoferrin, superoxide dismutase, and other enzymes—can become overwhelmed, especially with age or environmental burden.^2,3

In AMD, oxidative damage is also a central feature. The metabolic overload in retinal pigment epithelium (RPE) cells, constant light exposure, and mitochondrial dysfunction lead to the accumulation of oxidative DNA damage and chronic low-grade inflammation, which promote drusen formation and photoreceptor degeneration.⁴

Thus, in both DED and AMD, imbalanced ROS generation and impaired antioxidant defenses fuel a vicious cycle of inflammation and cellular injury.

Telomeres and biological aging

Telomeres, the repetitive DNA-protein “protective caps” at the ends of chromosomes, naturally shorten as cells divide. Telomeres, which shorten with oxidative and replicative stress, act as molecular clocks for cellular aging. When telomeres shorten below a critical length, cells enter senescence, triggering the release of pro-inflammatory cytokines and thereby promoting dysfunctional states. In AMD, findings from several studies have linked telomere length to disease risk. For example, women with shorter telomeres had higher odds of AMD, suggesting telomere attrition may mark systemic vulnerability.⁵

Interestingly, experimental activation of telomerase—the enzyme responsible for extending telomeres—in retinal cells reduced senescence, enhanced autophagy, and improved retinal function in models, suggesting a potential therapeutic approach.⁶

Although telomere shortening is not necessarily causal in DED, the same oxidative-inflammation loop that damages surface cells may accelerate cellular aging in lacrimal and, hypothetically, meibomian glands, contributing to tear dysfunction as we age. There are indications that telomere shortening occurs in diseased lacrimal glands. For example, a study comparing telomere length in lacrimal gland epithelial cells between patients with Sjögren syndrome and those with non-Sjögren dry eye found significantly shorter telomeres in the diseased group.⁷

The shared thread across DED, AMD, and telomere biology is the combined effect of oxidative stress and chronic inflammation in driving tissue-specific aging. In both diseases, the oxidative-inflammatory loop contributes to cumulative DNA damage; if this damage affects telomeres, it promotes senescence, altering tissue homeostasis.

Nutritional support: Modulating pathways of damage

Given the shared biology, nutritional strategies can potentially support both dry eye and AMD by reducing oxidative stress, dampening inflammation, and preserving cellular resilience.

• Antioxidants: Carotenoids such as lutein and zeaxanthin concentrate in the macula and filter blue light while neutralizing free radicals. The AREDS2 clinical trial (NCT00345176) data demonstrated that a supplement containing lutein and zeaxanthin, in conjunction with other antioxidants and minerals, reduces progression to advanced AMD.⁸
• Omega-3 and omega-6 fatty acids: These fatty acids modulate inflammation. For example, supplemental GLA and omega-3 fatty acids for 6 months improved ocular irritation symptoms, maintained corneal surface smoothness, and inhibited conjunctival dendritic cell maturation in patients with postmenopausal keratoconjunctivitis sicca.⁹

Clinical implications and future directions

• Holistic risk counseling: Eye care providers can explain to patients that dry eye and AMD share mechanistic roots in the biology of aging and are not a random coincidence. Emphasizing oxidative stress and cellular aging can help reinforce the importance of lifestyle interventions.
• Biomarker potential: Telomere length, while not yet a clinical test for eye disease, may emerge as a biomarker of systemic vulnerability. In the future, it could inform personalized prevention strategies.
• Targeted nutrition: Rather than using supplements ad hoc, evidence-based formulations—such as AREDS2 for AMD risk or GLA/EPA/DHA—can provide targeted benefits.
• Further research: More clinical trials are needed to prove whether interventions aimed at cellular aging (ie, telomerase activators) can meaningfully delay or mitigate both dry eye and AMD progression.

Conclusion

DED and macular degeneration converge around common pathways of oxidative damage, inflammation, and biological aging. Telomeres embody that convergence: Their shortening reflects cumulative stress and cellular wear. While we await more advanced therapies, nutritional support, anchored in antioxidants and anti‑inflammatory compounds, offers a practical, clinically grounded strategy to support ocular health and potentially slow the march of age‑related eye disease.

References

1. Hu R, Shi J, Xie CM, Yao XL. Dry eye disease: oxidative stress on ocular surface and cutting-edge antioxidants. Glob Chall. 2025;9(7):e00068. doi:10.1002/gch2.202500068

2. Hsueh YJ, Chen YN, Tsao YT, Cheng CM, Wu WC, Chen HC. The pathomechanism, antioxidant biomarkers, and treatment of oxidative stress-related eye diseases. Int J Mol Sci. 2022;23(3):1255. doi:10.3390/ijms23031255

3. Böhm EW, Buonfiglio F, Voigt AM, et al. Oxidative stress in the eye and its role in the pathophysiology of ocular diseases. Redox Biol. 2023;68:102967. doi:10.1016/j.redox.2023.102967

4. Datta S, Cano M, Ebrahimi K, Wang L, Handa JT. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Prog Retin Eye Res. 2017;60:201-218. doi:10.1016/j.preteyeres.2017.03.002

5. Koller A, Brandl C, Lamina C, et al. Relative telomere length is associated with age-related macular degeneration in women. Invest Ophthalmol Vis Sci. 2022;63(5):30. doi:10.1167/iovs.63.5.30

6. Blasiak J, Szczepanska J, Fila M, Pawlowska E, Kaarniranta K. Potential of telomerase in age-related macular degeneration-involvement of senescence, DNA damage response and autophagy and a key role of PGC-1α. Int J Mol Sci. 2021;22(13):7194. doi:10.3390/ijms22137194

7. Kawashima M, Kawakita T, Maida Y, et al. Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients. Mol Vis. 2011;17:1397-1404.

8. Age-Related Eye Disease Studies (AREDS/AREDS2). National Eye Institute. Updated December 27, 2024. Accessed December 5, 2025. https://www.nei.nih.gov/research/clinical-trials/age-related-eye-disease-studies-aredsareds2

9. Sheppard JD Jr, Singh R, McClellan AJ, et al. Long-term supplementation with n-6 and n-3 PUFAs improves moderate-to-severe keratoconjunctivitis sicca: a randomized double-blind clinical trial. Cornea. 2013;32(10):1297-1304. doi:10.1097/ICO.0b013e318299549c