lactoferrin and Keratoconus

Keratoconus (KC) is a corneal disorder whose etiology shares a close relationship with Lactoferrin (LTF) dysregulation and Toll-like Receptors 2 (TLR2) overexpression. This study shows how these two important biomarkers are clinically and molecularly interrelated, increasing knowledge about KC pathophysiology, and opening the door to future therapies. In this prospective clinical study, serum and tear LTF concentrations were quantified in 90 KC patients and 60 controls. A correlation analysis with multiple blood and tear immunoinflammatory mediators, and KC-associated tomographic parameters, was performed. An in vitro study using HEK-BlueTMhTLR2 cell cultures was also conducted to determine the expression and functionality of TLR2 under the influence of LTF treatment. As a result, a LTF decreased was observed in KC patients compared to controls (p < 0.0001), evidencing the strong correlation with TLR2 overexpression at systemic and ocular surface level, with inflammatory mediator upregulation and with KC severity. In stimulated cell cultures, TLR2 expression was decreased using 2 mg/mL of LTF. The levels of secreted embryonic alkaline phosphatase (SEAP) and interleukin-8 (IL-8) were also reduced in supernatants after LTF treatment. As conclusions, the dysregulation of LTF and TLR2 in the ocular surface of KC patients contributes to KC severity by maintaining a detrimental chronic immune−inflammatory state. The immunomodulatory properties of LTF on TLR2 expression suggest its potential as a therapeutic approach for KC.

Topics: Alkaline Phosphatase; Biomarkers; Humans; Interleukin-8; Keratoconus; Lactoferrin; Prospective Studies; Toll-Like Receptor 2

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.

Topics: Animals; Anti-Infective Agents; beta-Cyclodextrins; Cattle; Chickens; Chitosan; Cornea; Delayed-Action Preparations; Drug Delivery Systems; Humans; Keratoconus; Lactoferrin; Male; Nanoparticles; Rats, Sprague-Dawley

Topics: Adult; Anti-Infective Agents; Antioxidants; Apoproteins; Contact Lenses, Hydrophilic; Drug Carriers; Epithelial Cells; Female; Humans; Iron; Keratoconus; Kidney; Lactoferrin; Male; Oxidative Stress; Tears

Keratoconus is a degenerating disease of the eye which causes an irregularly shaped cornea leading to severe impairment of vision. Tear proteomics in keratoconus has been a topic of substantial discussion and speculation over many years. This study was designed to examine the levels of total protein, lactoferrin, secretory IgA and serum albumin in the tear film of people with keratoconus. Basal tears were collected using a capillary tube and corneal curvature was mapped using a topographer. Total protein in tears was estimated. The amount of regulated protein lactoferrin, constitutive protein sIgA and serum protein albumin was measured using specific ELISAs. The changes in protein concentrations in tears were correlated to the degree of corneal asphericity. There was a two-fold (p<0.0001) decrease in total protein levels between keratoconus (3.86 ± 1.62 mg/ml) and normal (7.00 ± 1.58 mg/ml) tears. The amount of lactoferrin (0.67 ± 0.28 vs. 1.13 ± 0.29 mg/ml) and secretory IgA (0.78 ± 0.36 vs. 1.70 ± 0.66 mg/ml) were significantly (p<0.0001) reduced in keratoconus tears. Variation in serum albumin levels between keratoconus (8.18 ± 4.72 μg/ml) and normal tears (11.66 ± 8.20 μg/ml) were not significant. The differences in total protein, lactoferrin and secretory IgA were not associated with contact lens wear, age, gender or atopy of subjects. The keratometry reading was negatively correlated to tear levels of total protein (r = -0.59, p < 0.01) lactoferrin (r = -0.40, p < 0.05) and secretory IgA (r = -0.34, p < 0.05). The tears of keratoconus subjects appear to have an altered protein profile, and one that might change with the severity of the disease. These findings may lead the way to understanding or monitoring disease progression.

Topics: Adult; Contact Lenses; Corneal Topography; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Eye Proteins; Female; Humans; Immunoglobulin A, Secretory; Keratoconus; Lactoferrin; Male; Serum Albumin; Specimen Handling; Tears; Young Adult