The pursuit of personalized medicine approaches for combating ocular diseases may be possible only through the development of nanotechnology platforms that include molecular-level engineering. Nanoparticle engineering is a common thread; herein, we attempt to show unmodified nanoparticles as well as interesting and representative biomimetic strategies can be used for specific diseases. Finally, through combining microelectromechanical and nanoelectromechanical manufacturing system strategies, interesting manufacturing and sensor development can be accomplished for early detection and, in some cases, treatment of ocular diseases.
Environmental factors, mainly oxidative stress and exposure to sunlight, induce the oxidation, cross-linking, cleavage, and deamination of crystallin proteins, resulting in their aggregation and, ultimately, cataract formation. Various denaturants have been used to initiate the aggregation of crystallin proteins in vitro. All of these regimens, however, are obviously far from replicating conditions that exist in vivo that lead to cataract formation. In fact, it is our supposition that only UV-B radiation may mimic the observed in vivo cause of crystallin alteration leading to cataract formation. This means of inducing cataract formation may provide the most appropriate in vitro platform for in-depth study of the fundamental cataractous fibril properties and allow for testing of possible treatment strategies. Herein, we showed that cataractous fibrils can be formed using UV-B radiation from α:β:γ crystallin protein mixtures. Characterization of the properties of formed aggregates confirmed the development of amyloid-like fibrils, which are in cross-β-pattern and possibly in anti-parallel β-sheet arrangement. Furthermore, we were also able to confirm that the presence of the molecular chaperone, α-crystallin, was able to inhibit fibril formation, as observed for ‘naturally’ occurring fibrils. Finally, the time-dependent fibrillation profile was found to be similar to the gradual formation of age-related nuclear cataracts. This data provided evidence for the initiation of fibril formation from physiologically relevant crystallin mixtures using UV-B radiation, and that the formed fibrils had several traits similar to that expected from cataracts developing in vivo.
Exfoliation syndrome is generally considered a progressive age‐related systemic disorder of the extracellular matrix, which is clinically characterized through the observation of flaky white aggregates on ocular tissues. Exfoliation syndrome is directly linked to exfoliative glaucoma in elderly patients, where it is known as the most common identifiable cause of open‐angle glaucoma. Despite the identification of various risk factors associated with exfoliation syndrome, the exact pathogenesis of this syndrome has not been fully elucidated. There is a growing number of genome‐wide association studies in different populations around the world to identify genetic factors underlying exfoliation syndrome. Besides variants in LOXL1 and CACNA1A genes, new loci have been recently identified which are believed to be associated with exfoliation syndrome. Among different genetic factors, functional variants might help to better understand mechanisms underlying this systemic disorder. Besides genetic factors, epigenetic regulation of different gene expression patterns has been thought to play a role in its pathogenesis. Other factors have been also considered to be involved in the development of exfoliation syndrome at cellular organelles level where mitochondrial impairment and autophagy dysfunction have been suggested in relation to exfoliation syndrome. This review addresses the most recent findings on genetic factors as well as cellular and molecular mechanisms involved in both the development and progression of exfoliation syndrome.
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