The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 μL triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography, and electroretinography. No serious side effects associated with the pretreatment were observed. These results indicate that surgical ILM peeling before AAV vector administration would be safe and useful for efficient transduction of the nonhuman primate retina and provide therapeutic benefits for the treatment of retinal diseases.
Objective:To examine the effects of rebamipide ophthalmic solution on the symptoms, signs, and cytokine concentrations in tear fluid among soft contact lens (SCL) wearers with Dry eye disease (DED).Methods:From November 2015 to June 2017, this open-label, single-arm study examined 40 eyes of 20 SCL wearers with DED who had been using daily disposable SCLs for >3 months (mean age, 30.0±8.33 years; range, 20–47 years). Signs, symptoms, and cytokine concentrations were assessed before and 4 weeks after starting 2% rebamipide ophthalmic solution 4 times/day. Dry eye disease was diagnosed according to: compromised tear dynamics (Schirmer test ≤5 mm or tear break-up time (TBUT) ≤5 sec); ocular surface abnormalities (positive vital staining with fluorescein or lissamine green); and presence of symptoms. Touch thresholds using a Cochet-Bonnet anesthesiometer were also determined for the cornea and conjunctivae. Symptoms were assessed using the 12-item Ocular Surface Disease Index questionnaire. Concentrations of cytokines in tear fluid were measured.Results:Significant improvements in signs were seen for TBUT, surface abnormalities, and touch thresholds. Ocular Surface Disease Index scores likewise improved significantly in all the 12 items. Of the cytokines measured, only interleukin-1β, interleukin-8, and monocyte chemotactic protein-1 were found in ≥60% of tear samples, with no significant differences in concentrations before and after rebamipide use.Conclusions:Rebamipide significantly improved all signs and symptoms in patients with DED who wore daily disposable SCLs. Rebamipide is effective for DED treatment with SCL wear.
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