Ocular problems have become one of the critical issues in the modern age. Among them, due to the heavy use of gadgets and computers and the over-sensitised immune response evoked by increasing environmental stimulants, dry eye disease (DED) is the most common ocular surface disease that severely compromises the quality of life. The prevalence of DED in Asia is approximately 20.1%, increasing with age (Cai et al., 2022). Moreover, it is estimated that the total cost of managing dry eye patients in the US healthcare system is USD$54.4 million per year (Yu et al., 2011). Hence, it has become a public health problem that cannot be neglected. Though it’s hard to conclude the specific causes of DED, accumulated studies agree that local inflammation of the cornea and conjunctiva and elevated immune response play major roles in its pathogenesis. As a consequence, it leads to abnormal secretion of the tissues from which the tear film forms, causing tear film instability, visual disturbances, and persistent discomfort. These tissues include the meibomian gland, lacrimal gland, and conjunctiva, which are responsible for lipid, aqueous layer, and mucin production, respectively. Currently, medical treatment for dry eyes usually focuses on topical drugs such as cyclosporine and glucocorticoids to reduce inflammation and immune response, or even only artificial tears (Jiang et al., 2022). However, these traditional treatments can only temporarily alleviate symptoms but not cure the root causes. Besides, frequent application of artificial tears is required whenever they dry up, and long-term use of topical steroids can lead to side effects such as increased eye pressure and cataracts, making these traditional treatments less than ideal (Wu et al., 2023). In recent years, regenerative medicine has rapidly developed, and scientists and eye specialists are developing new ways to treat DED. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles, which are rich in beneficial molecules, have multiple potentials including anti-inflammatory, tissue repair, tissue regeneration, and immune regulatory effects, making them the new hope in treating DED. Compared to MSCs, MSC-secreted vesicles, or so-called MSC-derived exosomes (MSC-Exos), are drawing more attention for their hypoimmunogenic, stable, and relatively safer characteristics. Moreover, the nano-scale size of MSC-Exos grants them privileges in penetrating through multiple tight barriers in eye structures, making them good carriers to deliver MSC-specific factors including proteins, DNA, RNA, and lipids to regulate cellular behaviours via modulating gene expression. Despite the challenges of identifying the specific mode of action (MOA) of MSC-Exos on DED treatment, there is hope on the horizon. As of today, a handful of scientific reports have shown the effectiveness of MSC-Exos on DED. For example, Ma and colleagues reported that Vitamin C (ascorbic acid) is a potent antioxidant that can eliminate excess reactive oxygen species (ROS), which are also considered one of the major causes of dry eye disease. Eye drops containing MSC-Exos coupled with vitamin C, which is a powerful antioxidant that can clear ROS, effectively improve corneal epithelium recovery and anti-inflammatory capacity, decrease corneal ROS, and restore tear secretion without adverse effects (Ma et al., 2023). MSC-Exos is emerging as a highly promising therapeutic option, providing the potential to address the root causes of DED effectively (Wu et al., 2022). Cai, Y., Wei, J., Zhou, J., & Zou, W. (2022). Prevalence and Incidence of Dry Eye Disease in Asia: A Systematic Review and Meta-Analysis. Ophthalmic Res, 65(6), 647-658. https://doi.org/10.1159/000525696 Jiang, Y., Lin, S., & Gao, Y. (2022). Mesenchymal Stromal Cell-Based Therapy for Dry Eye: Current Status and Future Perspectives. Cell Transplant, 31, 9636897221133818. https://doi.org/10.1177/09636897221133818 Ma, F., Feng, J., Liu, X., Tian, Y., Wang, W. J., Luan, F. X., Wang, Y. J., Yang, W. Q., Bai, J. Y., Zhang, Y. Q., & Tao, Y. (2023). A synergistic therapeutic nano-eyedrop for dry eye disease based on ascorbic acid-coupled exosomes. Nanoscale, 15(4), 1890-1899. https://doi.org/10.1039/d2nr05178h Wu, K. Y., Ahmad, H., Lin, G., Carbonneau, M., & Tran, S. D. (2023). Mesenchymal Stem Cell-Derived Exosomes in Ophthalmology: A Comprehensive Review. Pharmaceutics, 15(4). https://doi.org/10.3390/pharmaceutics15041167 Wu, K. Y., Chen, W. T., Chu-Bedard, Y. K., Patel, G., & Tran, S. D. (2022). Management of Sjogren's Dry Eye Disease-Advances in Ocular Drug Delivery Offering a New Hope. Pharmaceutics, 15(1). https://doi.org/10.3390/pharmaceutics15010147 Yu, J., Asche, C. V., & Fairchild, C. J. (2011). The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea, 30(4), 379-387. https://doi.org/10.1097/ICO.0b013e3181f7f363

Recently, the National Eye Institute (NEI, US) released an optimistic report stating that exosomes secreted by stem cells are protective to the retina. Exosomes are what doctors and biologists call microvesicles—tiny spheres of cellular membrane that cells use to communicate with each other. Exosomes are secreted and received by most cells within the body, and carry everything from genetic material and cellular signals to proteins. Researchers have known about exosomes for quite a while, but only recently started to understand their critical role in retinal health. Most recently, the National Eye Institute released an optimistic report that claims exosomes secreted by stem cells are protective to the retina. This new understanding could break ground for novel glaucoma treatments in the future. What role do exosomes play in the human eye? No one knows exactly how many roles exosomes play in the human body, but researchers have been studying the function of exosomes in the eye with particular interest due to their potential use as a drug delivery vehicle or as a therapy in and of themselves. A few studies indicate exosomes are critical in the health of the retina (specifically in the retinal pigment epithelium and retinal ganglion cells) and are essential for cellular repair. But how could these little bubbles of fat be so important to ocular health? The molecules within exosomes could act as signals to other cells and cause them to change their behavior from business-as-usual to repairing their surroundings—critical to preventing damage from building up within the eye from ocular stress.In one study, researchers found that retinal pigment epithelium cells are constantly under stress, which causes small amounts of damage to the nerve cells in the retina responsible for vision. Conditions like glaucoma also produce cellular damage in tiny amounts at a time. Therapeutically administered exosomes could potentially help decrease glaucoma damage. Could exosomes be used to treat glaucoma? In the study by the NEI, researchers fluorescently labeled exosomes and then tracked the cells the exosomes merged with upon their arrival. The result: optic nerve tissue sustained 60% less damage from ethanol when bolstered with added exosomes in comparison to those that weren’t. This is because exosomes in the retina carry microRNAs which are responsible for flipping cellular switches relating to repair. These findings suggest that supplementing other glaucoma therapies with an exosome treatment might act as an additional guard against vision loss, effectively beefing up the eye’s natural mechanisms for self- repair. The researchers also point out that exosomes are an appealing therapy option for glaucoma in comparison to other speculative treatments like stem cells, because they’re easy to produce, store, and deliver to patients safely via eye drops or injections. There’s even talk about developing a pill that could prompt extra exosome production to help with ocular repair. Another upside to this potential treatment is that exosomes are also unlikely to cause side effects in and of themselves, as they’re already common in the eye. Unlike eye drops with chemical additives, exosomes won’t cause red eyes, dryness, itchiness, or excessive tearing up when administered. For now, the biggest barrier between exosomes and the clinic is a lack of research into how exosomes are altered during the course of glaucoma. It’s not clear how exosomes are impacted by the progression of glaucoma, or how exosome supplementation would work long term for patients. Before exosomes can start to displace less comfortable or convenient glaucoma treatments, many studies remain to answer critical questions about their use. Adapted from Glaucoma Research Foundation. Click ME for the original article.