Purpose
To elucidate dysregulated proteins in keratoconus (KC) to provide a better understanding of the molecular mechanisms that lead to the development of the disease using sequential window acquisition of all theoretical mass spectra (SWATH-MS) as a protein quantification tool of the tear proteomic profile.
Methods
Prospective cross-sectional study that includes 25 keratoconic eyes and 25 healthy eyes. All participants underwent a clinical, tomographic, and aberrometric exam. Tear sample was collected using Schirmer strips and analyzed by liquid chromatography with tandem mass spectrometry. SWATH-MS was used as a quantification tool of the tear proteomic profile. The expression of the quantified proteins was compared between groups, and the biological and molecular functions of the dysregulated proteins as well as their functional relationships were studied by in silico analysis.
Results
A total of 203 proteins were quantified in tear samples of patients with KC and control participants, of which 18 showed differential expression between groups (
P
< 0.05). An increase in the expression of 7 proteins and a decrease in the expression of 11 proteins were observed. Protein–protein interactions and gene ontology analysis showed the involvement of these dysregulated proteins in structural, inflammatory-immune, iron homeostasis, oxidative stress, and extracellular matrix proteolysis processes.
Conclusions
Tear protein quantification has revealed the dysregulation of proteins involved in biological processes previously associated with KC. Among them, iron homeostasis should be highlighted as a relevant pathway in the KC pathophysiology, and it should be taken into account in the development of therapeutic targets to cope with tissue damage derived from iron accumulation and toxicity.
This
research study describes the design, optimization, and characterization
of two different types of chitosan-based nanoparticles as novel drug
delivery systems of a protein drug, lactoferrin. A preclinical consistent
base was obtained for both nanosystems, being considered as the first
pharmacological treatment for keratoconus as an alternative to current
invasive clinical methods. Both types of nanoparticles were obtained
via the ionotropic gelation technique. The size and morphology of
the nanoparticles were studied as a function of the preparation conditions.
A mean size of 180.73 ± 40.67 nm, a size distribution [polydispersity
index (PDI)] of 0.170 ± 0.067, and positive ζ-potential
values, ranging from 17.13 to 19.89 mV, were achieved. Lactoferrin
was successfully incorporated into both types of nanocarriers. In vitro release profiles showed a lactoferrin enhanced,
prolonged, and controlled delivery from the polymeric matrix. These
formulations also demonstrated no stability or cytotoxicity problems,
as well as appropriate mucoadhesive properties, with a high permanence
time in the ocular surface. Thus, both types of nanoparticles may
be considered as nanocarriers for the controlled release of lactoferrin
as novel topical ophthalmic drug delivery systems.
Alzheimer’s Disease (AD) is one of the main neurodegenerative diseases worldwide. Unfortunately, AD shares many similarities with other dementias at early stages, which impedes an accurate premortem diagnosis. Therefore, it is urgent to find biomarkers to allow for early diagnosis of the disease. There is increasing scientific evidence highlighting the similarities between the eye and other structures of the CNS, suggesting that knowledge acquired in eye research could be useful for research and diagnosis of AD. For example, the retina and optic nerve are considered part of the central nervous system, and their damage can result in retrograde and anterograde axon degeneration, as well as abnormal protein aggregation. In the anterior eye segment, the aqueous humor and tear film may be comparable to the cerebrospinal fluid. Both fluids are enriched with molecules that can be potential neurodegenerative biomarkers. Indeed, the pathophysiology of AD, characterized by cerebral deposits of amyloid-beta (Aβ) and tau protein, is also present in the eyes of AD patients, besides numerous structural and functional changes observed in the structure of the eyes. Therefore, all this evidence suggests that ocular changes have the potential to be used as either predictive values for AD assessment or as diagnostic tools.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.