Gentamicin Lessened Ocular Lesions in Junctional EB

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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antibiotic gentamicin

Topical administration of the antibiotic gentamicin to the eye restored the production of a key skin health protein called laminin 332 while rapidly lessening eye lesions in a woman with junctional epidermolysis bullosa (JEB), a study reports.

The study, “Topical gentamicin ointment induces LAMB3 nonsense mutation readthrough and improves corneal erosions in a patient with junctional epidermolysis bullosa,” was published as a letter to the editor of the journal Clinical & Experimental Ophthalmology.

Epidermolysis bullosa (EB) causes deficient wound healing and skin fragility. The eyes also are affected in all EB subtypes. In JEB, about 47.5% of patients have ocular involvement.

Currently, no cure is available for eye lesions in EB, with patients being provided with supportive care only.

JEB can be caused by mutations in the LAMB3 gene, which impair the production of functional laminin 332 protein, essential for skin integrity. Laminin 332 is a key component of the dermal-epidermal junction (DEJ), which is the region where the outermost layer of the skin, the epidermis, is attached to an inner skin layer called dermis.

Clinical testing has shown that, when applied over skin wounds, the antibiotic gentamicin can restore the production of laminin 332 and promote wound closure in EB patients. A study in cells also found that gentamicin can reverse the detrimental effects of mutations that cause low working laminin 332.

In the recent report, researchers in Taiwan described the case of a 26-year-old woman who often experienced the sensation of a foreign object in both eyes, and had right eye amblyopia (lazy eye).

The patient also had a history of generalized blistering and dystrophic (distorted and discolored) nails since childhood.

Optical coherence tomography, a non-invasive technique to image the eye’s retina — its innermost, light-sensitive part — showed the patient had scars in the cornea (the clear, outer layer) of both eyes.

Genetic testing revealed the presence of two mutations in the LAMB3 gene. One of the mutations had been reported previously, but the other was new. This new mutation likely leads to the production of a shorter, poorly functional laminin 332 protein, as suggested by additional tests.

Analysis of a skin biopsy showed a detached skin layer, and further analysis releaved an almost complete absence of laminin 332 at the DEJ, confirming the diagnosis of JEB.

For more than two years, the patient had been instructed to apply lubricating eye ointment at bedtime.

Because the corneal lesions were persistent, she was advised to use 0.3% topical gentamicin ointment once daily at bedtime.

Before treatment, the team found low levels of laminin 332 in conjunctial tissue, which lines the inside of the eyelids. However, within one week of treatment with gentamicin, cells located in the same region showed expression (production) of laminin 332.

Five weeks after beginning treatment, levels of this protein were up by nearly three times compared to before treatment. The corneal lesions were reduced, and the affected area was below 20%.

The Ocular Surface Disease Index, used to evaluate symptoms of ocular irritation, also further reflected clinical benefits.

Overall, the study shows that topical gentamicin ointment “restored laminin-332 expression in conjunctival cells and improved the ocular surface symptoms of a JEB patient,” the investigators wrote.