Abstract

Purpose: Keratoconus (KC) is characterized by progressive stromal thinning, with severity inversely related to Lysyl oxidase (LOX)levels. We aim to establish the safety and efficacy of recombinant adeno-associated virus (AAV)-mediated LOX gene delivery for KC.

Methods: Corneal lenticules(SMILE surgery) and cadaveric eyes(Unsuitable for transplant) were transduced with AAV.LOX and AAV.GFP(contro)l. LOX, MMP9, Collagen I, and Collagen IV were assessed using immunofluorescence and mRNA analysis. Atomic force microscopy (AFM) was employed to measure corneal strength post-therapy.

Results: AAV.LOX efficiently transduced corneal fibroblasts. Elevated LOX levels were associated with increased collagen production and reduced MMP9, indicating a reduction in inflammation. AFM revealed a higher elastic modulus post-AAV.LOX treatment.

Conclusion: Recombinant AAV-LOX therapy effectively halts corneal thinning and strengthens the cornea, offering a promising treatment avenue for KC.

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