Silicone hydrogels (SiHy), represent composite matrices composed of hydrophobic gas permeable silicone (Si) rich core and a surface enriched with hydrophilic polymer moieties. Their utilization in contact lens design requires number of SiHy properties (hydration, wettability, lubricity) to be optimized for the challenging conditions at the ocular surface. Typical limitations in literature are that (i) these properties are studied in isolation, monitoring only one parameter but not the rest of them, and (ii) measurements are performed with hydrated samples immediately after removal from storage solutions. Here we study the simultaneous evolution of critical material properties (evaporative loss of water, water contact angle, coefficient of friction) of different SiHy subjected to continuous blink-like desiccation/rehydration cycling. SiHy with wetting agents incorporated in their core (narafilcon A, senofilcon A) were particularly susceptible to extended desiccation. Stenfilcon A, a material with only 3% bulk Si content maintained its performance for 4 h of cycling, and delefilcon A (80% surface water content) resisted extended 8 h of desiccation/rehydration runs. Strong correlation exists between the evolution of SiHy wettability and lubricity at ≥4 h of blink-like cycling. Understanding the interplay between SiHy properties bears insights for knowledge based design of novel ophthalmic materials.
Lipids in complex, protein-enriched films at air/liquid interfaces reduce surface tension. In the absence of this benefit, the light refracting and immunoprotective tear film on eyes would collapse. Premature collapse, coupled with chronic inflammation compromising visual acuity, is a hallmark of dry eye disease affecting 7 – 10% of individuals worldwide. Although collapse seems independent of mutation (unlike newborn lung alveoli), selective proteome and possible lipidome changes have been noted. These include elevated tissue transglutaminase and consequent inactivation through C-terminal cross-linking of the tear mitogen lacritin, leading to significant loss of lacritin monomer. Lacritin monomer restores homeostasis via autophagy and mitochondrial fusion and promotes basal tearing. Here, we discover that lacritin monomer C-terminal processing, inclusive of cysteine, serine and metalloproteinase activity, generates cationic amphipathic α-helical proteoforms. Such proteoforms (using synthetic peptide surrogates) act like alveolar surfactant proteins to rapidly bind and stabilize the tear lipid layer. Immunodepletion of C-, but not N-terminal proteoforms nor intact lacritin, from normal human tears promotes loss of stability akin to human dry eye tears. Stability of these and dry eye tears is rescuable with C- but not N-terminal proteoforms. Repeated topical application in rabbits reveals a proteoform turnover time of 7 – 33 hours with gradual loss from human tear lipid that retains bioactivity without further processing. Thus, the processed C-terminus of lacritin that is deficient or absent in dry eye tears appears to play a key role in preventing tear film collapse and as a natural slow release mechanism that restores epithelial homeostasis.
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