Extracellular Vesicles of Tears and Ocular Surface: An Enigma.

Purpose: A stable ocular surface is crucial for maintaining ocular health by protecting against various infections. This is achieved by coordinated function of ocular structures (cornea, limbus, conjunctiva), innervation, and the tear film which forms a protective barrier over the ocular surface ensuring proper hydration, lubrication, and overall ocular comfort. This complex three-layered tear film secreted by different sources ensures its stability by adhesion to the corneal epithelium. Ocular surface fluid kinetics and tear secretion involve complex processes influenced by neural regulation, environmental factors, and molecular composition. Recent advances in cell biology and secretome has unravelled the mysteries of cellular cargo of almost every cell and system i.e. the extracellular vesicles (EVs) which facilitate intercellular communication. EVs are of different sizes, amongst which small EVs (sEVs) potentially are more informative than other EVs.

Methods: An extensive review of literature on sEVs in tears and ocular surface was conducted.

Results: Emerging literature on sEVs derived from ocular surface structures such as cornea and limbal stem cells contribute to corneal wound healing, regeneration and reduced fibrosis by the activation of specific proteins. A recent study documents that homeostasis between cornea and conjunctiva is maintained by the expression of specific genes triggering trans differentiation in diseased conditions. There is also mounting evidence on role of tear-derived sEVs in normal and diseased states. The approach in which tear layers secreted from three different sources form into a single tri-layered stable biofilm covering the entire ocular surface remains elusive. Hence not surprisingly, the tear sEVs therefore have been referred to as one entity and not attributed to any of the 3 different sources that they originate from.

Conclusion: This review attempts to present the recent concepts of sEVs, ocular surface, tears and highlight the gaps in our understanding of tear-derived exosomes and its potential role in homeostasis and disease conditions.