Lysyl oxidase augmentation a treatment option for thin corneas

A study was conducted by Pooja Khamar, PhD, FRCS, and colleagues to determine whether enhancing LOX expression in the cornea could benefit patients with a diagnosis of keratoconus.

Augmentation with lysyl oxidase (LOX), a cross-linking enzyme, in corneal tissues enhanced expression of collagens and decreased the matrix metalloproteinase (MMP)-9 levels, potentially making this treatment option useful for thin, poorly cross-linked corneas in patients with keratoconus, according to Pooja Khamar, PhD, FRCS. Khamar, a consultant in cataract and refractive services in the Department of Cornea and Refractive Surgery at Narayana Nethralaya Eye Institute in Bangalore, India, presented her results at the American Academy of Ophthalmology Annual Meeting.

Khamar conducted a study with her colleagues to determine whether enhancing LOX expression in the cornea, which appeared safe in mice, could benefit patients with a diagnosis of keratoconus. Khamar reported that LOX-expressing adeno-associated virus (AAV) vectors were generated and purified, whereas human donor corneal lenticules and mouse corneas were transduced with AAV LOX and AAV growth factor plus as controls. LOX, collagen type I, collagen type IV, and MMP-9 levels were measured in the corneal tissues.

Key study observations

The investigators reported that transduction of AAV appeared to be safe in mouse corneas. No haze developed, and no other associated problems were observed on the ocular surface.

The gene therapy vectors were functional and transduced the corneal fibroblasts in the human tissue and mouse corneas. Significantly higher levels of collagen expression were observed in association with higher LOX expression.

Higher levels of extracellular matrix and fibrosis genes were associated with LOX augmentation. Lower levels of MMP-9 were also observed.

According to investigators, AAV-mediated LOX therapy appeared to be well tolerated in this laboratory model and can be delivered to the eye effectively. LOX augmentation in corneal tissues enhanced expression of collagens and reduced MMP-9 levels. This therapy might block corneal thinning and therefore strengthen corneas with keratoconus. Investigators also pointed out that decreases in the MMP-9 levels might result in decreased inflammation associated with keratoconus. “These results indicate that LOX gene therapy might be a potential treatment for keratoconus,” Khamar concluded.

Pooja Khamar, PhD, FRCS

E: dr.poojakamar@gmail.com

Khamar is a consultant in cataract and refractive services in the Department of Cornea and Refractive Surgery at Narayana Nethralaya Eye Institute in Bangalore, India. She has no financial interest in this subject matter.