Recombinant Human Clusterin Seals Damage to the Ocular Surface Barrier in a Mouse Model of Ophthalmic Preservative-Induced Epitheliopathy

International Journal of Molecular Sciences · 2023 · 3 citations

• Medicine
• Ophthalmology
• Pharmacology

There is a significant unmet need for therapeutics to treat ocular surface barrier damage, also called epitheliopathy, due to dry eye and related diseases. We recently reported that the natural tear glycoprotein CLU (clusterin), a molecular chaperone and matrix metalloproteinase inhibitor, seals and heals epitheliopathy in mice subjected to desiccating stress in a model of aqueous-deficient/evaporative dry eye. Here we investigated CLU sealing using a second model with features of ophthalmic preservative-induced dry eye. The ocular surface was stressed by topical application of the ophthalmic preservative benzalkonium chloride (BAC). Then eyes were treated with CLU and sealing was evaluated immediately by quantification of clinical dye uptake. A commercial recombinant form of human CLU (rhCLU), as well as an rhCLU form produced in our laboratory, designed to be compatible with U.S. Food and Drug Administration guidelines on current Good Manufacturing Practices (cGMP), were as effective as natural plasma-derived human CLU (pCLU) in sealing the damaged ocular surface barrier. In contrast, two other proteins found in tears: TIMP1 and LCN1 (tear lipocalin), exhibited no sealing activity. The efficacy and selectivity of rhCLU for sealing of the damaged ocular surface epithelial barrier suggests that it could be of therapeutic value in treating BAC-induced epitheliopathy and related diseases.

Changes in Symptoms of Midday Fogging with a Novel Scleral Contact Lens Filling Solution

Optometry and Vision Science · 2020 · 23 citations

• Ophthalmology
• Medicine
• Optometry

SIGNIFICANCE: Midday fogging of scleral contact lenses requires frequent lens removal and reapplication for a large portion of lens wearers. Using a lens filling solution that mimics the composition of tears is hypothesized to have an impact on the production of material trapped under a scleral lens. PURPOSE: The purposes of this open-label study were to assess the safety of a scleral lens filling solution, which closely approximates the ionic concentration and pH of human tears, and to assess signs and symptoms of midday fogging with this formulation and with subjects' habitual sodium chloride solutions. METHODS: Existing scleral lens wearers with midday fogging (N = 22) were examined and completed surveys of symptoms. Subjects filled the concavity of their current lenses with test solution and were assessed immediately and approximately 4 hours later for safety monitoring. Test solution was dispensed and used for 5 to 9 days when subjects were reexamined and repeated the surveys. Biomicroscopy and anterior optical coherence tomography images were used to assess midday fogging objectively. RESULTS: The median (interquartile range) Ocular Surface Disease Index score decreased from 27.1 (21.7) U when using habitual filling solution to 9.1 (20.1) U when using the test solution (P = .006). Current Symptoms Survey findings with the test solution compared with habitual solution resulted in statistically significant decreases in burning/stinging (P = .04), grittiness/foreign body sensation (P = .01), dryness (P = .002), blurry/fluctuating vision (P = .002), and overall pain/discomfort (P = .006). Objective assessment of corneal staining and fogging revealed decreases that were not statistically significant in this small sample size. CONCLUSIONS: This study establishes the safety and subject tolerance of a scleral lens filling solution that mimics the ionic composition of human tears. Significant improvements in subjective ratings, although likely biased in this unmasked trial, suggest that further studies of the effectiveness of this solution in reducing midday fogging are warranted.