Adjunctive Thymosin Beta-4 Restores Visual Function and Nerve Integrity in Pseudomonas Keratitis

Bacterial keratitis is a severe corneal infection that can lead to permanent vision loss. Current treatments primarily focus on eradicating pathogens, but often overlook critical long-term outcomes like corneal nerve damage and impaired visual function. These sequelae significantly impact patient quality of life. Thymosin Beta-4 (Tβ4), a naturally occurring peptide, has demonstrated potent wound healing and tissue repair properties, including in corneal contexts. This study investigates whether Tβ4, as an adjunctive therapy, can bridge the gap in reparative outcomes by promoting nerve regeneration and restoring visual function.

Researchers induced bacterial keratitis in C57BL/6 mice by inoculating wounded corneas with Pseudomonas aeruginosa strain 19660. Topical treatments were administered three times daily, starting 24 hours post-infection. The treatment arms included PBS, Tβ4 monotherapy, ciprofloxacin monotherapy, and adjunctive Tβ4 + ciprofloxacin combination therapy. Ocular disease severity was assessed via clinical scoring. Visual recovery was quantified by measuring visual acuity (cycle/degree) and contrast sensitivity (%). Corneal sensitivity testing evaluated nerve function, and β-III tubulin immunofluorescence on flat mounts was used to visualize and quantify corneal nerves.

Adjunctive Tβ4 + ciprofloxacin treatment markedly improved visual acuity and contrast sensitivity compared with PBS, Tβ4 monotherapy, and ciprofloxacin monotherapy. The combination therapy also significantly enhanced corneal sensitivity, indicating improved nerve function. Furthermore, the study found robust evidence of nerve regeneration with the adjunctive treatment. This reparative effect was substantial:

Combination therapy restored nerve density and architecture to levels comparable to those observed in uninfected control corneas. These findings highlight that Tβ4's reparative properties extend beyond infection control, directly impacting critical physiological structures and functions often compromised by severe corneal infections.